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Citation: Paik, K.; Na, J.-I.; Huh,
C.-H.; Shin, J.-W. Particulate Matter
and Its Molecular Effects on Skin:
Implications for Various Skin Diseases.
Int. J. Mol. Sci. 2024,25, 9888.
https://doi.org/10.3390/
ijms25189888
Academic Editor: Ken-ichiro Inoue
Received: 30 July 2024
Revised: 9 September 2024
Accepted: 11 September 2024
Published: 13 September 2024
Copyright: © 2024 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
International Journal of
Molecular Sciences
Review
Particulate Matter and Its Molecular Effects on Skin:
Implications for Various Skin Diseases
Kyungho Paik 1,2 , Jung-Im Na 1,2 , Chang-Hun Huh 1,2 and Jung-Won Shin 1,2,*
1Department of Dermatology, Seoul National University Bundang Hospital, Seongnam 13620,
Republic of Korea; ndrdzdr@gmail.com (K.P.); vividna@gmail.com (J.-I.N.); chhuh@snu.ac.kr (C.-H.H.)
2
Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
*Correspondence: jungwonshin@snubh.org
Abstract: Particulate matter (PM) is a harmful air pollutant composed of chemicals and metals
which affects human health by penetrating both the respiratory system and skin, causing oxidative
stress and inflammation. This review investigates the association between PM and skin disease,
focusing on the underlying molecular mechanisms and specific disease pathways involved. Studies
have shown that PM exposure is positively associated with skin diseases such as atopic dermatitis,
psoriasis, acne, and skin aging. PM-induced oxidative stress damages lipids, proteins, and DNA,
impairing cellular functions and triggering inflammatory responses through pathways like aryl
hydrocarbon receptor (AhR), NF-
κ
B, and MAPK. This leads to increased production of inflammatory
cytokines and exacerbates skin conditions. PM exposure exacerbates AD by triggering inflammation
and barrier disruption. It disrupts keratinocyte differentiation and increases pro-inflammatory
cytokines in psoriasis. In acne, it increases sebum production and inflammatory biomarkers. It
accelerates skin aging by degrading ECM proteins and increasing MMP-1 and COX2. In conclusion,
PM compromises skin health by penetrating skin barriers, inducing oxidative stress and inflammation
through mechanisms like ROS generation and activation of key pathways, leading to cellular damage,
apoptosis, and autophagy. This highlights the need for protective measures and targeted treatments
to mitigate PM-induced skin damage.
Keywords: particulate matter; skin disease; atopic dermatitis; psoriasis; skin aging
1. Introduction
Air pollution caused by rapid industrialization and its effect on human health has
become a major global concern. Particulate matter (PM) is a major harmful air pollutant
composed of a complex mixture of solid and liquid particles that vary in size [
1
,
2
]. PM
originates from both natural and anthropogenic sources. It includes several chemical
constituents, such as nitrates, sulfates, elemental and organic carbon, organic compounds
(e.g., polycyclic aromatic hydrocarbons [PAHs]), biological compounds (e.g., endotoxins,
cell fragments), and metals (e.g., iron, copper, nickel, zinc, and vanadium) [
3
]. Based
on size, PM is classified as ultrafine (particles with a diameter < 0.1
µ
m), fine (particles
with a diameter < 2.5
µ
m: PM2.5), and coarse (particles with a diameter < 10
µ
m: PM10).
PM can penetrate the airways from the nasal passages to the alveoli where gas exchange
occurs, leading to numerous adverse health effects [
3
]. PM induces pro-inflammatory
effects by generating reactive oxygen species (ROS), leading to oxidative stress [
4
,
5
]. ROS
production triggers the release of inflammatory cytokines, resulting in inflammation and
tissue damage [
6
,
7
]. PM can cause irregular heartbeat, aggravated asthma, decreased lung
function, and increased respiratory symptoms, as well as premature death in individuals
with heart or lung disease [8–10].
As the outermost layer of the body, the skin is at a greater risk of exposure to PM.
Unlike the respiratory mucosa, the skin has a stratum corneum composed of dead ker-
Int. J. Mol. Sci. 2024,25, 9888. https://doi.org/10.3390/ijms25189888 https://www.mdpi.com/journal/ijms
Int. J. Mol. Sci. 2024,25, 9888 2 of 18
atinocytes embedded in a lipid matrix, serving as the strongest barrier against environ-
mental stressors, including PM. However, a previous study demonstrated that PM could
penetrate barrier-disrupted skin and hair follicles [
11
]. Moreover, PM is associated with the
aggravation of skin disorders, including atopic dermatitis (AD), eczema, skin aging, and
pigmentation [12–14].
With increasing evidence, numerous review articles have emerged
that summarize the effects of PM on various skin conditions [
2
,
12
,
15
,
16
]. However, most
existing reviews have primarily focused on epidemiologic findings. Although some stud-
ies have explored biological mechanisms, none have systematically organized how PM
contributes to the specific pathogenesis of individual diseases. This review explores the re-
lationship between PM and various skin diseases and examines the molecular mechanisms
involved, including disease-specific pathways.
2. Methodology
We performed a comprehensive literature search across databases including PubMed,
Medline, and Scopus. Initially, we used key search terms such as “particulate matter”
combined with “skin diseases” or “skin health” to identify specific skin conditions as-
sociated with PM exposure. Epidemiological studies, narrative reviews, and systematic
reviews were included in this phase. Based on the strength of the evidence, four skin
conditions—atopic dermatitis, psoriasis, acne, and skin aging—were selected. Subse-
quently, we conducted a second search using “particulate matter” in combination with
terms like “skin disease”, “skin physiology”, “atopic dermatitis”, “psoriasis”, “acne”, “skin
aging”, and “skin pigmentation.” At this stage, only laboratory studies using skin cells or
review articles summarizing laboratory findings were included.
3. Basic Molecular Mechanisms of Particulate Matter (PM)-Induced Skin Damage
PM primarily induces skin diseases through oxidative stress, which leads to inflam-
matory responses and barrier disruption [
15
]. A significant concern is whether PM can
penetrate the skin barrier and reach viable cell layers, thereby affecting skin biology. PM
can penetrate the epidermis through hair follicles or a disrupted stratum corneum [
11
].
Although PM particles do not penetrate, they adhere to the skin surface and release soluble
components, such as gases or ions, causing harmful effects [
11
,
15
]. This section describes
the general molecular mechanisms underlying PM-induced skin damage.
3.1. Penetration of PM into the Skin
A study using a mouse model found that PM could penetrate the skin following
barrier disruption induced by tape stripping, infiltrating both the barrier-disrupted interfol-
licular epidermis and the intact follicular epidermis, resulting in cutaneous inflammation
(Figure 1A) [
11
]. In addition, multimodal nonlinear optical imaging in an ex vivo human
skin model showed deeper PM penetration with increased tape stripping, leading to higher
pro-inflammatory cytokine secretion [
17
]. Another study using a reconstructed human
epidermis model demonstrated that PM particles penetrated the stratum corneum after
24 h and reached deeper layers after 48 h [18].
Int. J. Mol. Sci. 2024,25, 9888 3 of 18
Int. J. Mol. Sci. 2024, 25, x FOR PEER REVIEW 3 of 21
Figure 1. Primary molecular mechanisms of PM-induced skin damage. (A) PM can penetrate the
skin, infiltrating both the barrier-disrupted interfollicular epidermis and the intact follicular epider-
mis. (B) PM activates cellular signaling pathways such as AhR and TLR, leading to increased ROS
production, while PM itself also generates ROS. ROS from PM causes oxidative stress, damaging
lipids, proteins, and DNA, impairing cellular functions, and causing apoptosis. It activates NF-κB,
promoting cytokines (TNF, IL-1α, IL-1β), adhesion molecules (ICAM1), and enzymes (COX2). ROS
also activate MAPK pathways (ERK, JNK, p38), leading to inflammatory responses in skin.
3.2. Aryl Hydrocarbon Receptor Activation
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that
mediates the skin response to environmental pollutants, including PM IL (Figure 1B) [19].
AhR is ubiquitously expressed in all skin cell types and plays crucial roles in epidermal
differentiation, barrier function, and the maintenance of skin homeostasis [20–22]. PAHs,
the components bound to the surface of PM, act as ligands for AhR. Upon binding, AhR
is activated and translocated to the nucleus, where it binds to the AhR nuclear translocator
(ARNT) [23]. The AhR–ligand–ARNT complex promotes the transcription of the cyto-
chrome p450 (CYP) family, including CYP1A1, CYP1A2, and CYP1B1 [24]. CYP enzymes
metabolize PAHs, and the resulting metabolites can cause cell damage through the for-
mation of DNA and protein adducts or ROS generation. PM exposure upregulates CYP
mRNA and protein expression, both in vitro and in vivo [18,23,25–29]. Additionally, PM
can induce ROS production via the AhR/p47 phox/nicotinamide adenine dinucleotide
phosphate hydrogen (NADPH) oxidase (NOX)2 pathway [30–34].
3.3. Oxidative Stress Induced by PM
Oxidative stress is one of the primary mechanisms through which PM harms the skin.
ROS, which are highly reactive molecules involved in oxygen metabolism, play a central
Figure 1. Primary molecular mechanisms of PM-induced skin damage. (A) PM can penetrate
the skin, infiltrating both the barrier-disrupted interfollicular epidermis and the intact follicular
epidermis. (B) PM activates cellular signaling pathways such as AhR and TLR, leading to increased
ROS production, while PM itself also generates ROS. ROS from PM causes oxidative stress, damaging
lipids, proteins, and DNA, impairing cellular functions, and causing apoptosis. It activates NF-
κ
B,
promoting cytokines (TNF, IL-1
α
, IL-1
β
), adhesion molecules (ICAM1), and enzymes (COX2). ROS
also activate MAPK pathways (ERK, JNK, p38), leading to inflammatory responses in skin.
3.2. Aryl Hydrocarbon Receptor Activation
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that
mediates the skin response to environmental pollutants, including PM IL (Figure 1B) [
19
].
AhR is ubiquitously expressed in all skin cell types and plays crucial roles in epidermal
differentiation, barrier function, and the maintenance of skin homeostasis [
20
–
22
]. PAHs,
the components bound to the surface of PM, act as ligands for AhR. Upon binding, AhR
is activated and translocated to the nucleus, where it binds to the AhR nuclear translo-
cator (ARNT) [
23
]. The AhR–ligand–ARNT complex promotes the transcription of the
cytochrome p450 (CYP) family, including CYP1A1, CYP1A2, and CYP1B1 [
24
]. CYP en-
zymes metabolize PAHs, and the resulting metabolites can cause cell damage through the
formation of DNA and protein adducts or ROS generation. PM exposure upregulates CYP
mRNA and protein expression, both
in vitro
and
in vivo
[
18
,
23
,
25
–
29
]. Additionally, PM
can induce ROS production via the AhR/p47 phox/nicotinamide adenine dinucleotide
phosphate hydrogen (NADPH) oxidase (NOX)2 pathway [30–34].
3.3. Oxidative Stress Induced by PM
Oxidative stress is one of the primary mechanisms through which PM harms the skin.
ROS, which are highly reactive molecules involved in oxygen metabolism, play a central role
Int. J. Mol. Sci. 2024,25, 9888 4 of 18
in this process (Figure 1B) [
35
]. PM induces ROS generation directly and indirectly. When
antioxidant defenses of the skin, such as superoxide dismutase, catalase, and glutathione
peroxidase, are overwhelmed by excessive ROS, oxidative stress is induced [36].
3.3.1. Reactive Oxygen Species Formation by PM
PM directly induces the production of ROS through redox-active components, such as
transition metals, which catalyze ROS generation [
37
]. PM surfaces contain organic com-
pounds, such as PAHs, that form quinones upon metabolic activation by CYP enzymes [
38
].
These quinones undergo redox cycling, leading to the production of superoxide anion radi-
cals and hydrogen peroxide in the skin cells. PM also indirectly induces ROS production
by activating cellular signaling pathways. A key pathway is the generation of ROS through
the AhR, as previously mentioned. Additionally, pattern recognition receptors, such as
toll-like receptors (TLRs) on keratinocytes, recognize PM and initiate intracellular signaling.
PM induces a direct interaction between TLR5 and NOX4, leading to the production of
ROS and the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells
(NF-
κ
B)–interleukin (IL)-6 pathway. This signaling cascade results in the expression of in-
flammatory cytokines, which contribute to the inflammatory response and exacerbate skin
damage [
31
]. Additionally, PM exposure disrupts mitochondrial function, causing electron
leakage from the electron transport chain and enhancing intracellular ROS levels [
15
]. Ad-
ditionally, PM-induced endoplasmic reticulum (ER) stress contributes to ROS production
by disrupting protein folding and inducing an unfolded protein response [39–41].
3.3.2. Lipid Peroxidation, Protein Oxidation, and DNA Damage
ROS, particularly hydroxyl radicals, react with lipids in cell membranes, initiating
a chain reaction that damages polyunsaturated fatty acids. This process generates lipid
peroxide and reactive aldehydes, such as malondialdehyde and 4-hydroxynonenal. Lipid
peroxidation compromises cell membrane integrity and fluidity and impairs cellular func-
tions and signaling pathways. Oxidative damage affects the barrier function of the skin,
leading to increased permeability and susceptibility to environmental aggressors and
allergens [42,43].
Additionally, ROS, including hydroxyl radicals and superoxide anions, oxidize amino
acid residues in proteins, resulting in the formation of carbonyl groups and disulfide
bonds. This oxidative modification affects the protein structure and function, leading to
the formation of protein aggregates and degradation products. Protein oxidation impairs
critical cellular functions and disrupts enzymatic activity, receptor signaling, and structural
integrity. In the skin, oxidative damage can compromise the extracellular matrix (ECM)
and cellular cytoskeleton, leading to skin conditions [44].
PM-induced ROS production can also lead to significant DNA damage in the skin
cells. ROS can directly attack DNA molecules, causing strand breaks, base modifications,
and cross-linking [
45
]. Oxidative DNA damage activates cellular repair mechanisms and
stress responses; however, excessive or persistent damage can overwhelm these systems,
resulting in mutations and apoptosis that can cause skin diseases [15,39].
3.3.3. PM-Induced Cell Death by Mitochondrial Damage and Endoplasmic
Reticulum Stress
Oxidative stress induced by PM can lead to the activation of apoptosis and pro-
grammed cell death [
46
]. Excessive ROS disrupt the electron transport chain of the mito-
chondria, causing electron leakage and further ROS production. Oxidative stress results in
mitochondrial membrane disruption, mitochondrial DNA damage, and impaired ATP syn-
thesis [
18
,
39
,
47
]. It also leads to the release of proapoptotic factors, such as cytochrome C,
and the activation of caspase 3, caspase 9, and poly (ADP-ribose) polymerase [
39
,
41
,
48
–
50
].
These events exacerbate injury and promote the apoptosis of skin cells, further contributing
to skin damage. In addition, PM-induced ROS causes ER stress by interfering with protein
folding and homeostasis [
39
,
51
]. PM2.5 upregulates the protein levels of CCAAT enhancer-
Int. J. Mol. Sci. 2024,25, 9888 5 of 18
binding protein homologous protein, a transcription factor that mediates ER stress-induced
apoptosis [
39
,
41
,
52
]. ER stress is also associated with autophagy. PM exposure upregulates
light-chain 3B II, a protein involved in the initiation of autophagosome formation [26,39].
3.4. Inflammatory Responses
Activation of the inflammatory cascade is another crucial mechanism by which PM
affects skin diseases via ROS production (Figure 1B). PM-induced ROS can activate NF-
κ
B, a key transcription factor that induces a large number of inflammatory genes [
53
,
54
].
Its targets include chemokines and cytokines, such as tumor necrosis factor (TNF), IL
1-alpha (IL-1
α
), IL-1
β
, and C-X-C motif chemokine ligand (CXCL8), crucial for skin
inflammation [
25
,
55
]. Other targets include adhesion molecules, such as intercellular
adhesion molecule 1 (ICAM1), and enzymes, such as cyclooxygenase (COX)2 and inducible
nitric oxide synthase (iNOS) [
18
,
27
,
55
,
56
]. COX2 is essential for prostaglandin E2 formation
from arachidonic acid in membrane phospholipids [
57
]. In addition, PM-induced ROS can
activate mitogen-activated protein kinase (MAPK) and its members, including extracellular
signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, and transcription factor
adaptor protein 1 [
58
]. The exposure of fibroblasts and keratinocytes to PM induces the
MAPK pathway through the phosphorylation of ERK, JNK, and p38 [
32
,
33
,
53
,
59
]. PM
exposure also stimulates inflammasome activation. A study has shown that PM-treated
human immortalized epidermal cells exhibit elevated mRNA levels of NOD-like-receptor
containing a pyrin domain 1 (NLRP1), an inflammasome-related gene, and increased
protein levels of IL-1
β
, a key downstream factor of NLRP1 [
60
]. This activation contributes
to an inflammatory response in the skin, further exacerbating skin diseases and damage.
3.5. Summary
PM can penetrate disrupted and intact skin, causing inflammation It induces ROS
generation both directly and indirectly. Directly, PM itself produces ROS. Indirectly, PM
activates cellular signaling pathways such as AhR and TLR, leading to increased ROS
production. ROS from PM overwhelm skin defenses, causing oxidative stress, damaging
lipids, proteins, and DNA, and impairing cellular functions. PM exposure activates NF-
κ
B complexes, promoting cytokines (TNF, IL-1
α
, IL-1
β
, CXCL8), adhesion molecules
(ICAM1), and enzymes (COX2, iNOS). ROS also activate MAPK pathways (ERK, JNK, p38),
increasing inflammation and leading to mitochondrial and ER stress, resulting in apoptosis
and autophagy.
4. Skin Diseases Associated with PM and Disease-Specific Molecular Mechanisms
Numerous epidemiological studies have demonstrated that PM is associated with
various skin conditions (Table 1). Additionally, several experimental studies have proposed
potential mechanisms by which PM affects the pathogenesis of specific skin diseases
(Table 2, Figure 2). This section explores how PM influences disease-specific pathways at
the molecular level for each condition, focusing on representative skin diseases that have
been epidemiologically related to PM exposure.
Table 1. Summary of epidemiological studies on the association between outdoor particulate matter
and skin diseases.
Skin
Disease Study Location PM Design Age (Y)
Sample Size
(no.) Major Findings
Atopic
dermatitis
(AD)
Gu et al.,
2023 [61]UK
PM2.5
PMcoarse
PM10
prospective
cohort study 40–70 337,910
The medium (HR, 1.182, p= 0.003) and high (HR, 1.359,
p< 0.001) air pollution mixture was significantly
associated with incident AD compared with the low
pollution group.
PM2.5 absorbance accounted for the majority
proportion of effects for air pollution mixtures.
Keller et al.,
2022 [62]USA PM2.5 Cohort study ≤18 16,089,050 PM2.5 was not associated with atopic eczema when
adjusted for NO2.
Int. J. Mol. Sci. 2024,25, 9888 6 of 18
Table 1. Cont.
Skin
Disease Study Location PM Design Age (Y)
Sample Size
(no.) Major Findings
Park et al.,
2022 [63]
South
Korea
PM2.5
PM10
Population-
based
retrospective
cohort study
0–75 209,168
PM2.5 (HR, 1.420; 95% CI, 1.392–1.448; for 1 µg/m3)
and PM10 (HR, 1.333, 95% CI, 1.325–1.341; for
1µg/m3) showed a significant positive association
with AD incidence.
Ye et al.,
2022 [64]China PM2.5
PM10
Time-series
study All 34,633
Exposure to PM2.5 and PM10 worsened symptoms of
AD, with PM10 being more detrimental than PM2.5.
Children aged 0–7 years and women were the most
vulnerable to particulate matter.
Park et al.,
2021 [65]
South
Korea
PM2.5
PM10
Time-series
study All 23,288,000
A 10
µ
g/m
3
increase in PM2.5 and PM10 led to patient
visit increases of 2.71% (95% CI: 0.76–4.71; p< 0.01) and
2.01% (95% CI: 0.92–3.11; p< 0.001), respectively.
Wang et al.,
2021 [66]China PM2.5
PM10
Time-series
study All 45,094
An increase of 10
µ
g/m
3
in PM2.5 was associated with
a 1.1% (95% CI: 0.6%–1.7%) rise in dermatitis/eczema
visits at lag 0–1 days.
Bae, et al.,
2020 [67]
South
Korea
PM2.5
PM10
Time-series
study All 513,870
The risk of AD-related visits was associated with higher
PM10 (RR, 1.009, 95% CI: 1.007–1.012).
Tang et al.,
2017 [68]Taiwan PM2.5
PM10
Cross-
sectional study
≥20 1023
PM2.5 was significantly associated with AD (aOR, 1.05,
95% CI:1.02–1.08).
Kim et al.,
2017 [69]
South
Korea PM10 Panel study 0–5 177
A 10 µg/m3increase in PM10 was associated with a
3.2% (95% CI: 1.5–4.9%) increase in visits on the
same day.
Liu et al.,
2016 [70]China PM10 Cross-
sectional study
4–6 3358 No significant association between PM10 and
childhood eczema.
Wang et al.,
2016 [71]China PM2.5
PM10
Cross-
sectional study
Kindergarten
children 2661 No significant association.
Eczema Sun et al.,
2022 [72]China PM10 Cross-
sectional study
Preschool
age 2399 PM10 concentrations were positively associated with
eczema symptoms (p= 0.03).
Hüls et al.,
2019 [73]Germany PM2.5
PM10 Cohort study ≥55 834
Baseline PM10 and PM2.5 levels were associated with
incidence of nonatopic eczema (OR, 1.356, 95% I:
1.004–1.831, OR, 1.454, 95%CI: 1.064–1.987).
Wang et al.,
2019 [74]China PM2.5 Time-series
study ≥18 1,966,991
A 10 µg/m3increase in PM2.5 on the current day was
associated with a 0.30% (95% CI: 0.28–0.33%) change in
the number of hospital visits.
Li et al.,
2018 [75]China PM10 Time-series
study All 14,000,000
An increase of 10 µg/m3in PM10 corresponded to an
increasing RR of 1.0024 at lag 0, which represented an
increase of 0.24% in eczema outpatient visits.
Shah et al.,
2016 [76]US PM10 Cross-
sectional study
3 m–58 m 128
A comparison of subjects with and without eczema
showed a difference in the natural log of PM collected
from the PIPER air sampling (p= 0.049).
Psoriasis
Bellinato
et al., 2022
[77]
Italy PM2.5
PM10
Cross-over and
cross-sectional
study
All 369
Exposure to mean PM10 over 20 µg/m3and mean
PM2.5 over 15
µ
g/m
3
in the 60 days before assessment
were associated with a higher risk of PASI 5 or greater
point worsening (aOR, 1.55, 95% CI: 1.21–1.99 and aOR,
1.25, 95% CI: 1.0–1.57).
Wu et al.,
2022 [78]China PM2.5 Time-series
study All 500,266
A same-day increase of 10 µg/m3in PM2.5
concentrations was associated with a 0.29% (95%
confidence interval: 0.26–0.32%) increase in daily
outpatient visits for psoriasis. Female and older
patients appeared to be more sensitive to the effects of
PM2.5 (p< 0.05).
Lee et al.,
2022 [79]Korea PM2.5
PM10
Longitudinal
study All
Poulation of
7 major
cities in
Korea
PM2.5 and PM10 had no impact on hospital visits of
psoriasis patients.
Park et al.,
2021 [65]Korea PM2.5
PM10
Time-series
study All 23,288,000
Concentrations of PM2.5 and PM10 were significantly
associated with a increase in psoriasis patient visits,
with increases of 1.46% (95% CI: 0.53–2.40%; p< 0.01)
and 1.50% (95% CI: 0.99–2.02%; p< 0.001), respectively.
Acne Li et al.,
2022 [80]China PM2.5 Time-series
study All 120,842
A 10
µ
g/m
3
increase in PM2.5 concentration at lag 0–7
was associated with a 1.71% (95% CI: 1.06–2.36%) rise
in acne outpatient visits, with individuals aged 25 and
older being more susceptible than those under 25 years.
Int. J. Mol. Sci. 2024,25, 9888 7 of 18
Table 1. Cont.
Skin
Disease Study Location PM Design Age (Y)
Sample Size
(no.) Major Findings
Li et al., 2021
[81]China PM10 Time-series
study All 71,625
The association between PM10 and acne visits was
significant only in middle-aged and older adults (over
30 years old), with a 10 µg/m3increase in PM10 at lag
0–3 corresponding to a 0.46% (95% CI: 0.08–0.84%)
increase in acne visits.
El Haddad
et al., 2021
[82]
Lebanon PM2.5
PM10
Cross-
sectional study
18–55 372 No association was found between PM2.5, PM10,
and acne.
Liu et al.,
2018 [83]China PM2.5
PM10
Time-series
study All 59,325
PM10 and PM2.5 showed significant effects on the
number of outpatient visits for acne vulgaris after
additionally adjusting for SO2 (PM10: RR, 1.023,
p< 0.05; PM2.5: RR, 1.016, p< 0.05).
Skin
Aging
Huang et al.,
2022 [84]Taiwan PM2.5
PM10
Cross-
sectional study
30–74 389
High PM10 and PM2.5 concentrations were both
associated with high brown spot scores (coefficient β,
0.48, p= 0.00, and coefficient β, 0.86, p= 0.00,
respectively).
Peng et al.,
2017 [85]China PM2.5 Cross-
sectional study
40–90 400
People living in districts with low PM2.5 levels tended
to have a lower number of spots on their cheeks and the
backs of their hands (OR, 0.403, 95% CI: 0.239–0.679;
OR, 0.263, 95% CI: 0.146–0.441). No association with
seborrheic keratosis.
Vierkotter
et al., 2010
[14]
Germany PM2.5
PM10
Cross-
sectional study
70–80 400
There were 22% more spots on the forehead and 20%
more spots on the cheeks per increase of one
interquartile range (IQR) of PM2.5 absorbance (OR,
1.22, 95% CI: 1.03–1.45, OR, 1.20, 95% CI: 1.03–1.40).
PM = particulate matter, OR = odds ratio, aOR = adjusted odds ratio, RR = relative risk, HR = hazard ratio,
CI = confidence interval.
Table 2. Summary of the impact of PM on specific skin conditions at a molecular level.
Skin Disease Study Model PM Type PM Application Main Findings
Atopic dermatitis
(AD)
Roh et al.,
2024 [42]
AD-like triple cell model
SRM 1649b - 25 µg/cm2, systemic
-↑IL-6, IL-1β, and IL-1α
-↓IL-10
-↓mRNA level of filaggrin and loricrin
Kwack et al.,
2022 [43]
DNCB-induced AD
mouse model (BALB/c)
PM10-like
ERM71 CZ120 - 100 µg/mL, topical
-↑Serum IgE
-↑Epidermal thickness and mast cell count
-↑
IL-1
β
, IL-4, IL-6, IL-17
α
, IL-25, IL-31 and
TSLP
-↓Loricrin and filaggrin
Kim et al.,
2021 [86]
- Hairless mice (Crl:
SKH1-Hrhr)
- HSE
- HEK
PM2.5 from Seoul,
Korea
- 1~10 ng/mL and
100 ng/mL
- Topical in the mouse
study, systemic in the
cell study and 3D skin
model
-↓FLG, loricrin, keratin-1, desmocollin-1,
and corneodesmosin
-↑TEWL
Bae et al.,
2020 [67]
- OXA-induced AD
mouse model
(BALB/c)
- HaCaT cells
SRMs 1648a and
1649b
- 100 µg/cm3airborne
in the mouse study
- 50 and 25 µg/cm2,
topical in the cell
study
-↑Epidermal and dermal thickness
-↑Dermal inflammation
-↓mRNA level of filaggrin, involucrin,
loricrin, claudin-1, and ZO-1
Woo et al.,
2020 [87]
- OVA-induced AD
mouse model
- (BALB/c)
PM10
SRM 2787 - 2.5 mg/mL, topical
-↑Skin severity scores, TEWL and
epidermal thickness
-↑S100A9,SPRR2D,SPRR2B,S100A8,
SPRR2A3 gene expression
Li et al., 2020
[88]
- Murine keratinocyte
cell line PAM212 PM2.5 - 20, 50 and 100
µg/mL, systemic -↑mRNA and protein level of TSLP
Hidaka et al.,
2017 [89]- AhR-CA mice Diesel exhaust
particles - 1mg/mL, topical
-↑AD-like lesions
- Epidermal hyper-innervation and
inflammation
- Hypersensitivity to pruritus
Sadakane
et al., 2013
[90]
- PiCl-induced AD
mouse model
(NC/Nga)
Diesel exhaust
particles - Topical
- Worsening of AD-like skin lesions
-↑IL-4, keratinocyte chemoattractant, and
neutrophils
Int. J. Mol. Sci. 2024,25, 9888 8 of 18
Table 2. Cont.
Skin Disease Study Model PM Type PM Application Main Findings
Psoriasis Wang et al.,
2022 [91]
- Psoriasis mouse
model (C57BL/6)
- KRT17 knockdown
psoriasis cell model
PM2.5 - 183.80 µg/m3,
airborne
- More severe psoriatic skin lesions
-↑KRT17 protein
-↑AKT/mTOR/HIF-1αsignaling pathway
-↑S100a8 and S100a7a
- Specific agonist of AKT (740Y-P) reversed
the decreased neovascularization induced
by KRT17 knockdown through
AKT/mTOR/HIF-1αsignaling pathway
Cheng et al.,
2020 [92]
- hESC-based
differentiation models
Ultrafine carbon
nanopowder
- 1, 10 and 100 ng/mL,
1 and 10 µg/mL,
systemic
-↓SOX2 expression
-↓Keratinocyte differentiation
-↑
Inflammation and psoriasis-related genes
(IL-1β,IL-6,CXCL1,CXCL2,CXCL3,CCL20,
CXCL8, and S100A7 and S100A9)
Kim et al.,
2017 [93]
- NHEK
- HSE PM2.5
- 25 µg/mL, systemic
in the cell study
- 50 µg/mL topical in
the 3D skin model
-↑
Pro-inflammatory cytokines and psoriatic
skin disease-related genes in keratinocytes
-↓keratin-10, desmocollin 1, claudin, and
IL-36γin HSE
-↑S100A7 and S100A8 in HSE
Acne Noh et al.,
2022 [94]- NHEK SRM 1649b - 10 µg/cm2, systemic
-↑mRNA and protein levels of
proinflammatory cytokines, COX2, TLR4,
and the phosphorylation of NF-κB
Kwack et al.,
2022 [95]
-
Human sebocytes and
ORS cell
- Acne mouse model
(HR-1)
PM10-like
(ERM-CZ120)
- 100 µg/mL, systemic
in the cell study and
topical in the animal
study
- IL-1α, IL-1β, IL-6, IL-8, TNF-α, MMP-1 in
sebocytes and ORS cells
-↑C. acnes-induced inflammatory nodule
diameter and thickness in a mouse model
-↑IL-1α, IL-1β, IL-6, IL-8, TNF-α, MMP-1,
MMP-3, and MMP-12 in inflammatory
nodules in the mouse model
-↑sebum production in inflammatory
nodules in the mouse model
-↑PPARγ, SCD, SREBP1a, and SREBP1c in
cultured sebocytes
Skin aging Ahn et al.,
2022 [96]
- C57BL/6 mice
- NHM
- HSE
- SRM 1648a
- 25 µg/mL, topical in
the mouse study,
systemic in the cell
study and 3D skin
model
-↑Melanin production in melanocytes,
mouse model, and human skin model
-↑IRE1αsignaling pathway
Moon et al.,
2022 [97]
- NHM
- NHK
- HSE
- HDF
- PM10, from
Seoul, Korea
- SRM 1648a and
1649b
- 100 µg/mL, systemic
-↑mRNA level of IL-1α, IL-1β, IL-8, and
MMP-3 in in keratinocytes
-↑melanin synthesis in keratinocyte:
melanocyte (1:1) co-culture
-↑Epidermal melanin pigmentation in ex
vivo skin tissue
-↑mRNA level of SCF and ET-1 in
keratinocytes
-↑mRNA level of MMP-1, MMP-2, and
MMP-3 in dermal fibroblasts treated with
the conditioned media obtained from
keratinocytes exposed to local PM10
-Ko et al.,
2020 [98]
- NHM
- HaCaT cells
- HDF
PM2.5 (NIST 1650b)
- 50 ppm, systemic
-↑ET-1 and PGE2 in
keratinocyte/melanocyte coculture
-↑NF-κB, cysteine-rich protein 61, and
MMP-1, ↓Procollagen type I in
fibroblast/keratinocyte co-culture
Kim et al.,
2019 [99]
- HaCaT cells
- HDF SRM 1648a and
1649b
- 50 µg/cm2for 1648a
and 25 µg/cm2for
1649b, systemic
-↑IL-1αand IL-1βin keratinocytes
-↑
MMP1 and COX2 in fibroblasts co-culture
with keratinocytes
PM = particulate matter, IL = interleukin, DNCB = 1-chloro-2,4-dinitrobenzene, OXA = oxazolone,
OVA = ovalbumin,
HaCaT cell = human, adult, low calcium, high temperature, HEK = human epidermal primary
keratinocyte, CA-AhR = constitutively active aryl hydrocarbon receptor, KRT17 = keratin 17, hESC = human
embryonic stem cell, HSE = human skin equivalent, NHEK = normal human epidermal keratinocyte, ORS = outer
root sheath, NHM = normal human epidermal melanocyte, NHK = normal human epidermal keratinocyte,
HDF = human
dermal fibroblast, MMP = matrix metalloproteinase, FLG = filaggrin, TEWL = transepidermal wa-
ter loss, ZO-1 = zonula occludens-1, TSLP = thymic stromal lymphopoietin, AKT = protein kinase B, mTOR = mam-
malian target of rapamycin, HIF-1a = hypoxia inducible factor 1 subunit alpha, SOX-1 = SRY-Box transcription
factor 1, CCL, CXCL = chemokine ligand, COX2 = cyclooxygenase, TLR = toll-like receptor, NF-
κ
B = Nuclear
factor kappa B, PPAR
γ
= peroxisome proliferator-activated gamma receptors, SREBP = Sterol regulatory element
binding proteins, IRE1
α
= Inositol-requiring transmembrane kinase/endoribonuclease 1
α
, SCF = stem cell factor,
ET-1 = endothelin 1, PGE = prostaglandin E.
Int. J. Mol. Sci. 2024,25, 9888 9 of 18
Int. J. Mol. Sci. 2024, 25, x FOR PEER REVIEW 12 of 21
Figure 2. A schematic representation of the molecular effects of particulate maer on skin diseases,
illustrating the disease-specific pathways involved. TEWL = transepidermal water loss, FLG = fil-
aggrin, LOR = loricrin, IL = interleukin, TRPV = transient receptor potential vanilloid, AKT = protein
kinase B, mTOR = mammalian target of rapamycin, HIF-1a = hypoxia inducible factor 1 subunit
alpha, CCL, CXCL = chemokine ligand, IRE1α = Inositol-requiring transmembrane, kinase/endori-
bonuclease 1α, SCF = stem cell factor, ET-1 = endothelin 1, MMP = matrix metalloproteins, COX =
cyclooxygenase, ECM = extracellular matrix.
4.1. Atopic Dermatitis
AD, also known as atopic eczema, is a chronic relapsing inflammatory skin disorder
characterized by intense pruritus, erythema, scaling, and lichenification. It predominantly
affects the flexural areas in children and adults and the face and extensor surfaces of in-
fants. Both genetic predisposition and environmental factors are known to be contributing
factors in the development of AD [100,101]. To date, most studies on PM and skin diseases
have focused on AD (Table 1). In a prospective cohort study using the UK Biobank, PM2.5
absorbance (black carbon) had a substantial effect on the incidence of adult-onset AD [61].
Other studies have also shown that increased levels of PM10 and/or PM2.5 are positively
associated with increased patient visits for AD [65,66,102]. However, some studies have
shown no association between PM and AD. For example, PM2.5 was not associated with
AD when adjusting for nitrogen dioxide in a study conducted in the USA [62].
The key pathogenesis of AD centers on skin barrier dysfunction and immune dysreg-
ulation. Skin barrier dysfunction is primarily associated with genetic abnormalities, par-
ticularly in the essential membrane protein filaggrin (FLG). Immune dysregulation in AD
is characterized by a dominant Th2 axis involving cytokines such as IL-4, IL-13, IL-5,
thymic stromal lymphopoietin (TSLP), and IL-31, along with elevated Th17/IL-23 path-
ways and increased IgE levels [103]. In many previous experimental studies, PM has been
shown to trigger molecular pathways associated with the pathogenesis of AD (Table 2,
Figure 2). In mouse models, PM induces or worsens AD-like skin lesions [87,89,90]. Addi-
tionally, PM exposure has been found to increase epidermal thickness and promote the
infiltration of dermal inflammatory cells, including mast cells, which are characteristic
histopathological features of AD [43,67,89]. Additionally, PM treatment upregulates the
expression of various inflammatory cytokines, such as IL-1α, IL-1β, IL-4, IL-6, IL-17α, IL-
25, IL-31, and TSLP, in both mouse and in vitro cell models [42,43,88]. PM also induces
Figure 2. A schematic representation of the molecular effects of particulate matter on skin diseases, il-
lustrating the disease-specific pathways involved. TEWL = transepidermal water loss, FLG = filaggrin,
LOR = loricrin, IL = interleukin, TRPV = transient receptor potential vanilloid, AKT = protein kinase
B, mTOR = mammalian target of rapamycin, HIF-1a = hypoxia inducible factor 1 subunit alpha, CCL,
CXCL = chemokine ligand, IRE1
α
= Inositol-requiring transmembrane, kinase/endoribonuclease 1
α
,
SCF = stem cell factor, ET-1 = endothelin 1, MMP = matrix metalloproteins, COX = cyclooxygenase,
ECM = extracellular matrix.
4.1. Atopic Dermatitis
AD, also known as atopic eczema, is a chronic relapsing inflammatory skin disorder
characterized by intense pruritus, erythema, scaling, and lichenification. It predominantly
affects the flexural areas in children and adults and the face and extensor surfaces of infants.
Both genetic predisposition and environmental factors are known to be contributing factors
in the development of AD [
100
,
101
]. To date, most studies on PM and skin diseases have
focused on AD (Table 1). In a prospective cohort study using the UK Biobank, PM2.5
absorbance (black carbon) had a substantial effect on the incidence of adult-onset AD [
61
].
Other studies have also shown that increased levels of PM10 and/or PM2.5 are positively
associated with increased patient visits for AD [
65
,
66
,
102
]. However, some studies have
shown no association between PM and AD. For example, PM2.5 was not associated with
AD when adjusting for nitrogen dioxide in a study conducted in the USA [62].
The key pathogenesis of AD centers on skin barrier dysfunction and immune dys-
regulation. Skin barrier dysfunction is primarily associated with genetic abnormalities,
particularly in the essential membrane protein filaggrin (FLG). Immune dysregulation in
AD is characterized by a dominant Th2 axis involving cytokines such as IL-4, IL-13, IL-5,
thymic stromal lymphopoietin (TSLP), and IL-31, along with elevated Th17/IL-23 pathways
and increased IgE levels [
103
]. In many previous experimental studies, PM has been shown
to trigger molecular pathways associated with the pathogenesis of AD (Table 2, Figure 2).
In mouse models, PM induces or worsens AD-like skin lesions [
87
,
89
,
90
]. Additionally, PM
exposure has been found to increase epidermal thickness and promote the infiltration of
dermal inflammatory cells, including mast cells, which are characteristic histopathological
features of AD [
43
,
67
,
89
]. Additionally, PM treatment upregulates the expression of various
inflammatory cytokines, such as IL-1
α
, IL-1
β
, IL-4, IL-6, IL-17
α
, IL-25, IL-31, and TSLP, in
Int. J. Mol. Sci. 2024,25, 9888 10 of 18
both mouse and
in vitro
cell models [
42
,
43
,
88
]. PM also induces barrier dysfunction and
increases transepidermal water loss by downregulating essential epidermal proteins, such
as filaggrin and loricrin [
42
,
43
,
67
,
86
]. These proteins are crucial for skin differentiation and
barrier functions, and their reduced expression compromises skin integrity. Activated AhR
causes excessive epidermal innervation of transient receptor potential vanilloid 1 neurons
by inducing artemin. This results in a decreased threshold for itching, leading to persistent
itching and scratching, commonly observed in AD [89].
4.2. Psoriasis
Psoriasis is a chronic immune-mediated inflammatory skin disorder characterized
by well-demarcated erythematous plaques with silvery scales that commonly affect the
extensor surfaces, scalp, and nails. Epidemiological studies investigating the association
between PM exposure and psoriasis have reported inconsistent results (Table 1). Several
studies have found that PM2.5 and PM10 are positively associated with hospital visits for
psoriasis or flare-ups [
65
,
78
,
104
]. In contrast, another study reported no significant effect
of PM on psoriasis [
79
]. Further studies are required to quantify the clinical effects of PM
exposure on psoriasis.
The pathogenesis of psoriasis involves a complex interplay between genetic predispo-
sition and environmental triggers, leading to dysregulated keratinocyte proliferation and
inflammatory cell infiltration, primarily mediated by T helper (Th) 17 and Th1 cells [
105
].
Differentiated and activated Th17 cells secrete IL-17A, stimulating keratinocytes and caus-
ing epidermal hyperproliferation in psoriasis [
106
]. Keratinocytes then release antimicro-
bial peptides, such as LL-37 and S100-alarmins [
107
]. Notably, S100a7 (psoriasin) and
S100a8 (calgranulin A) are highly upregulated in psoriatic lesions, driving dysregulated
keratinocyte differentiation, neutrophil chemotaxis, abnormal angiogenesis, and increased
inflammation [
108
,
109
]. In a mouse model, PM2.5 exposure induced more severe pso-
riatic skin lesions and increased the expression of keratin 17 protein as well as S100a8
and S100a7a [
91
]. In addition, protein kinase B (Akt)/mammalian/mechanistic target
of rapamycin (mTOR)/hypoxia-inducible factor (HIF)-1
α
/vascular endothelial growth
factor (VEGF) signaling pathways were highly activated in psoriatic skin after PM2.5
exposure (Table 2, Figure 2). In the
in vitro
model, a specific agonist of AKT (740Y-P)
reversed the decreased neovascularization induced by KRT17 knockdown through the
AKT/mTOR/HIF-1
α
signaling pathway
in vitro
. This suggests that PM2.5 exposure could
promote the development and progression of psoriasis through KRT17-dependent activa-
tion of the AKT/mTOR/HIF-1
α
signaling pathway [
91
]. In other studies, PM disrupted
SOX2 expression and keratinocyte differentiation and upregulated pro-inflammatory cy-
tokines and psoriatic skin disease-related genes, including IL-1
β
, IL-6, CXCL1, CXCL2,
CXCL3, CCL20, CXCL8, and S100A7 and S100A9 [
92
,
93
]. PM2.5 treatment also led to a
decrease in skin barrier markers, including keratin 10, desmocollin 1, and claudin 1, in a
three-dimensional skin model [93].
4.3. Acne
Acne is a common inflammatory skin disorder that affects the pilosebaceous unit
and is characterized by comedones, papules, pustules, nodules, and cysts. It primarily
occurs on the face, chest, and back, and predominantly affects adolescents and young
adults. Exposure to high levels of PM has been associated with an increased number of
acne outpatient visits, particularly in urban areas with significant air pollution; however,
the results were not consistent across all studies (Table 1, [
80
–
83
]). Further epidemiological
studies are required to elucidate the long-term effects of PM on acne.
The primary pathogenesis of acne involves increased sebum production, follicular
keratinization, inflammation, and colonization by Cutibacterium acnes (C. acnes) [
110
,
111
].
C. acnes triggers the release of pro-inflammatory cytokines, such as IL-1, IL-6, IL-8, and
tumor necrosis factor-alpha (TNF-
α
), from keratinocytes, sebocytes, and immune cells. This
bacterium also activates the TLR pathways in immune and skin cells, further amplifying
Int. J. Mol. Sci. 2024,25, 9888 11 of 18
the inflammatory response [
112
]. This activation leads to the recruitment of neutrophils
and other immune cells to the site, contributing to inflamed acne lesions such as papules,
pustules, and nodules. To date, a few experimental studies have explored the molecular
effects of PM on specific acne pathogenesis (Table 2, Figure 2). PM exposure was shown
to increase the diameter and thickness of C. acnes-induced inflammatory nodules and
upregulate inflammatory biomarkers, including IL-1
α
, IL-1
β
, IL-6, IL-8, TNF-
α
, matrix
metalloproteinase (MMP)-1, MMP-3, and MMP-12, in a mouse model [
95
]. It also enhanced
the expression of peroxisome proliferator-activated receptor
γ
, stearoyl-CoA desaturase,
sterol regulatory element-binding protein (SREBP) 1a, and SREBP1c in cultured sebocytes,
increasing sebum production in the mouse model [
95
]. In addition, PM was shown to
increase the phosphorylation of NF-
κ
B in C. acnes- and PGN-treated keratinocytes, and
increase COX2 and TLR4 levels [
94
]. This suggests that PM may exacerbate acne symptoms
by amplifying the inflammatory response.
4.4. Aging Skin
Aging skin is characterized by structural and functional changes that lead to visible
signs, such as wrinkles and pigmentation. Factors such as ultraviolet radiation, oxidative
stress, and environmental pollutants accelerate the aging process. These alterations re-
flect the cumulative effects of intrinsic aging and extrinsic factors on skin integrity and
appearance. Several epidemiologic studies have shown that exposure to PM2.5 and PM10
is associated with increased pigmented spots and more prominent wrinkles [
14
,
84
]. Fur-
thermore, another study demonstrated the relationship between PM2.5 and the occurrence
of senile lentigo, but not with seborrheic keratosis [
85
]. These studies underscore the
significant effect of PM on skin aging by contributing to changes in pigmentation and
wrinkle formation.
The primary pathomechanism of wrinkle formation involves the degradation of ex-
tracellular matrix (ECM) proteins in the dermis, including collagen, fibronectin, elastin,
and proteoglycans, leading to decreased skin elasticity and firmness. Dermal fibroblasts
are responsible for the synthesis and degradation of ECM proteins. Notably, as aging
progresses, collagen degradation increases while its production decreases, exacerbating
the loss of skin structure and contributing to wrinkle formation [
113
–
115
]. Interestingly,
although fibroblasts alone are not directly affected by PM exposure, they exhibit increased
expression of phospho-NF
κ
B, MMP-1, and COX2, along with decreased expression of
procollagen I when co-cultured with keratinocytes (Table 2, Figure 2) [
98
,
99
]. This phe-
nomenon can be understood within the context of “inflammaging”, a term describing the
chronic, low-grade inflammation contributing to aging. When keratinocytes are exposed to
PM, they initiate inflammatory responses that include the release of cytokines and other
signaling molecules. These inflammatory signals can activate nearby fibroblasts, even if the
fibroblasts themselves are not directly exposed to PM. The activation of NF-
κ
B in fibroblasts,
a key regulator of inflammatory responses, leads to the upregulation of MMP-1, an enzyme
responsible for collagen degradation, and COX2, an enzyme involved in inflammatory
processes. The reduction in procollagen I expression further exacerbates the breakdown of
the extracellular matrix, contributing to a loss of skin integrity and accelerating aging.
Another key aspect of skin aging is pigmentation changes, such as age spots and un-
even skin tone, which result from the overproduction and uneven distribution of melanin.
These changes are often exacerbated by sun exposure and photoaging [
116
]. PM has been
shown to increase melanin production in human keratinocytes,
in vivo
mouse models,
and ex vivo human skin models [
96
,
97
]. This process is associated with the upregula-
tion of the inositol-requiring enzyme type 1 (IRE1)
α
signaling pathway, indicating an
association with ER stress [
96
] (Table 2, Figure 2). Furthermore, one study showed that
PM exposure increased the mRNA expression of melanogenic cytokines, such as stem
cell factor and endothelin-1, in keratinocytes and enhanced melanin synthesis in a ker-
atinocyte:melanocyte (1:1) co-culture [
97
]. This indicates that melanocytes alone or in
Int. J. Mol. Sci. 2024,25, 9888 12 of 18
combination with keratinocytes increase melanin production when exposed to PM, leading
to increased skin pigmentation.
4.5. Summary
Numerous epidemiological studies have demonstrated a relationship between various
inflammatory skin diseases, such as AD, eczema, psoriasis, acne, and aging skin, and PM
exposure. At the molecular level, PM exposure exacerbates AD by inducing inflamma-
tory responses, barrier disruption, and pruritus. In psoriasis, PM disrupts keratinocyte
differentiation and upregulates pro-inflammatory cytokines. In acne, PM enhances inflam-
matory biomarkers and increases sebum production in inflammatory nodules. Regarding
skin aging, PM degrades ECM proteins and upregulates MMP-1 and COX2 in fibroblast-
keratinocyte co-cultures. Additionally, PM boosts melanin production through the IRE1
α
pathway and increases melanogenic cytokines, leading to increased skin pigmentation.
5. Discussion
The molecular impact of PM on skin diseases is an area of growing interest, with
many studies highlighting the complex interactions between environmental pollutants
and dermatological conditions. However, while the evidence linking PM exposure to skin
diseases such as AD, psoriasis, acne, and skin aging is compelling, several limitations
in the existing research need to be addressed to understand these mechanisms and their
implications for public health fully.
One of the primary limitations of current studies is the variability in experimental
models used to study the effects of PM. Many studies rely on
in vitro
models or animal
studies, which, while valuable, may not fully capture the complexity of human skin
responses to PM. Additionally, these models often use isolated components of PM, which
may not reflect the full spectrum of environmental pollutants. Another limitation is the lack
of long-term studies assessing the chronic effects of low-level PM exposure, which is more
representative of real-world conditions. Most studies have focused on acute, high-dose
exposures, which may not accurately depict the cumulative impact of PM on skin over
time. Furthermore, there is limited research on the interaction between PM and other
environmental factors, such as ultraviolet irradiation, temperature, and humidity, which
could modulate the effects of PM on the skin. The role of individual genetic susceptibility
in response to PM exposure remains underexplored, particularly in different skin types
and conditions.
To address these gaps, future research should develop more sophisticated
in vitro
and
in vivo
models that closely mimic human skin, incorporating the full range of envi-
ronmental factors that influence the effects of PM. Long-term epidemiological studies are
needed to understand better the chronic effects of PM exposure on skin health, especially
in populations with varying levels of exposure and genetic backgrounds. Additionally,
research should aim to elucidate how PM interacts with other environmental factors, such
as UV radiation, to exacerbate skin conditions.
One emerging topic for future research is exploring the skin microbiome’s role in
modulating PM’s effects. It has been shown that the composition of the skin microbiome is
dependent on the living environment (polluted and less polluted) [
117
–
119
]. Furthermore,
these changes have been correlated with skin pigmentation dysfunction in individuals
residing in polluted environments, highlighting the impact of pollution on skin health
and the microbiome [
117
]. Given the interplay between the skin microbiome and PM,
targeting the microbiome presents a novel therapeutic approach to mitigating the effects of
PM on the skin. Probiotic and prebiotic treatments, designed to restore a healthy micro-
biome balance, could help strengthen the skin’s barrier function and reduce inflammation.
For instance, anti-pollutant treatment strategies targeting the microbiome could involve
beneficial bacteria like Roseomonas mucosa, which has shown promise in treating AD by
modulating lipid production and TNF signaling. This approach could also have potential in
psoriasis, where R. mucosa has demonstrated preclinical efficacy, suggesting that microbial
Int. J. Mol. Sci. 2024,25, 9888 13 of 18
manipulation may offer therapeutic benefits in managing skin diseases exacerbated by
environmental pollutants, including PM [
120
]. Additionally, understanding the specific
microbial changes induced by PM exposure could lead to developing personalized skincare
products that cater to individual microbiome profiles. This personalized approach could
optimize the skin’s resilience against environmental pollutants by supporting a healthy
and balanced microbiome.
In conclusion, while significant progress has been made in understanding the molec-
ular impact of PM on skin diseases, there is still much to be explored. Addressing the
limitations of previous studies through more advanced research methods, exploring newly
emerging molecular targets, and considering potential therapeutic strategies will be crucial
in developing practical approaches to mitigate the harmful effects of PM on skin health.
Author Contributions: Conceptualization, J.-W.S. and K.P.; methodology, J.-W.S.; investigation,
J.-W.S., J.-I.N., C.-H.H. and K.P.; data curation, J.-W.S.; writing—original draft preparation, J.-W.S. and
K.P.; writing—review and editing, J.-W.S., J.-I.N., C.-H.H. and K.P.; supervision, J.-W.S. All authors
have read and agreed to the published version of the manuscript.
Funding: This study was supported by grant no. 02-2024-0015 from the Seoul National University
Bundang Hospital Research Fund.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Data sharing not applicable—no new data generated.
Conflicts of Interest: The authors declare no conflicts of interest.
References
1.
Carlsten, C.; Melen, E. Air pollution, genetics, and allergy: An update. Curr. Opin. Allergy Clin. Immunol. 2012,12, 455–460.
[CrossRef] [PubMed]
2.
Kim, K.E.; Cho, D.; Park, H.J. Air pollution and skin diseases: Adverse effects of airborne particulate matter on various skin
diseases. Life Sci. 2016,152, 126–134. [CrossRef] [PubMed]
3.
Kim, K.H.; Kabir, E.; Kabir, S. A review on the human health impact of airborne particulate matter. Environ. Int. 2015,74, 136–143.
[CrossRef]
4. Cooper, D.M.; Loxham, M. Particulate matter and the airway epithelium: The special case of the underground? Eur. Respir. Rev.
2019,28, 190066. [CrossRef]
5.
van Klaveren, R.J.; Nemery, B. Role of reactive oxygen species in occupational and environmental obstructive pulmonary diseases.
Curr. Opin. Pulm. Med. 1999,5, 118–123. [CrossRef] [PubMed]
6.
Moller, P.; Folkmann, J.K.; Forchhammer, L.; Brauner, E.V.; Danielsen, P.H.; Risom, L.; Loft, S. Air pollution, oxidative damage to
DNA, and carcinogenesis. Cancer Lett. 2008,266, 84–97. [CrossRef]
7.
Aggarwal, B.B. Apoptosis and nuclear factor-kappa B: A tale of association and dissociation. Biochem. Pharmacol. 2000,60,
1033–1039. [CrossRef]
8.
Cadelis, G.; Tourres, R.; Molinie, J. Short-term effects of the particulate pollutants contained in Saharan dust on the visits of
children to the emergency department due to asthmatic conditions in Guadeloupe (French Archipelago of the Caribbean). PLoS
ONE 2014,9, e91136. [CrossRef]
9.
Correia, A.W.; Pope, C.A., 3rd; Dockery, D.W.; Wang, Y.; Ezzati, M.; Dominici, F. Effect of air pollution control on life expectancy
in the United States: An analysis of 545 U.S. counties for the period from 2000 to 2007. Epidemiology 2013,24, 23–31. [CrossRef]
10.
Fang, Y.; Naik, V.; Horowitz, L.W.; Mauzerall, D.L. Air pollution and associated human mortality: The role of air pollutant
emissions, climate change and methane concentration increases from the preindustrial period to present. Atmos. Chem. Phys.
2013,13, 1377–1394. [CrossRef]
11.
Jin, S.P.; Li, Z.; Choi, E.K.; Lee, S.; Kim, Y.K.; Seo, E.Y.; Chung, J.H.; Cho, S. Urban particulate matter in air pollution penetrates
into the barrier-disrupted skin and produces ROS-dependent cutaneous inflammatory response
in vivo
.J. Dermatol. Sci. 2018,91,
175–183. [CrossRef] [PubMed]
12.
Ngoc, L.T.N.; Park, D.; Lee, Y.; Lee, Y.C. Systematic Review and Meta-Analysis of Human Skin Diseases Due to Particulate Matter.
Int. J. Environ. Res. Public. Health 2017,14, 1458. [CrossRef] [PubMed]
13. Kim, J.; Kim, E.H.; Oh, I.; Jung, K.; Han, Y.; Cheong, H.K.; Ahn, K. Symptoms of atopic dermatitis are influenced by outdoor air
pollution. J. Allergy Clin. Immunol. 2013,132, 495–498.e491. [CrossRef]
14.
Vierkotter, A.; Schikowski, T.; Ranft, U.; Sugiri, D.; Matsui, M.; Kramer, U.; Krutmann, J. Airborne particle exposure and extrinsic
skin aging. J. Investig. Dermatol. 2010,130, 2719–2726. [CrossRef] [PubMed]
Int. J. Mol. Sci. 2024,25, 9888 14 of 18
15.
Chao, L.; Feng, B.; Liang, H.; Zhao, X.; Song, J. Particulate matter and inflammatory skin diseases: From epidemiological and
mechanistic studies. Sci. Total Environ. 2023,905, 167111. [CrossRef]
16.
Puri, P.; Nandar, S.K.; Kathuria, S.; Ramesh, V. Effects of air pollution on the skin: A review. Indian. J. Dermatol. Venereol. Leprol.
2017,83, 415–423. [CrossRef]
17.
Lee, E.S.; Kim, S.; Lee, S.W.; Jung, J.; Lee, S.H.; Na, H.W.; Kim, H.J.; Hong, Y.D.; Park, W.S.; Lee, T.G.; et al. Molecule-Resolved
Visualization of Particulate Matter on Human Skin Using Multimodal Nonlinear Optical Imaging. Int. J. Mol. Sci. 2021,22, 5199.
[CrossRef]
18.
Magnani, N.D.; Muresan, X.M.; Belmonte, G.; Cervellati, F.; Sticozzi, C.; Pecorelli, A.; Miracco, C.; Marchini, T.; Evelson, P.;
Valacchi, G. Skin Damage Mechanisms Related to Airborne Particulate Matter Exposure. Toxicol. Sci. 2016,149, 227–236.
[CrossRef] [PubMed]
19.
Fernandez-Gallego, N.; Sanchez-Madrid, F.; Cibrian, D. Role of AHR Ligands in Skin Homeostasis and Cutaneous Inflammation.
Cells 2021,10, 3176. [CrossRef]
20.
Esser, C.; Bargen, I.; Weighardt, H.; Haarmann-Stemmann, T.; Krutmann, J. Functions of the aryl hydrocarbon receptor in the skin.
Semin. Immunopathol. 2013,35, 677–691. [CrossRef]
21.
van den Bogaard, E.H.; Podolsky, M.A.; Smits, J.P.; Cui, X.; John, C.; Gowda, K.; Desai, D.; Amin, S.G.; Schalkwijk, J.; Perdew,
G.H.; et al. Genetic and pharmacological analysis identifies a physiological role for the AHR in epidermal differentiation. J.
Investig. Dermatol. 2015,135, 1320–1328. [CrossRef] [PubMed]
22.
van den Bogaard, E.H.; Bergboer, J.G.; Vonk-Bergers, M.; van Vlijmen-Willems, I.M.; Hato, S.V.; van der Valk, P.G.; Schroder, J.M.;
Joosten, I.; Zeeuwen, P.L.; Schalkwijk, J. Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis. J. Clin. Investig.
2013,123, 917–927. [CrossRef] [PubMed]
23.
Dijkhoff, I.M.; Drasler, B.; Karakocak, B.B.; Petri-Fink, A.; Valacchi, G.; Eeman, M.; Rothen-Rutishauser, B. Impact of airborne
particulate matter on skin: A systematic review from epidemiology to
in vitro
studies. Part. Fibre Toxicol. 2020,17, 35. [CrossRef]
[PubMed]
24.
Furue, M.; Takahara, M.; Nakahara, T.; Uchi, H. Role of AhR/ARNT system in skin homeostasis. Arch. Dermatol. Res. 2014,306,
769–779. [CrossRef]
25.
Ruiz Martinez, M.A.; Peralta Galisteo, S.; Castan, H.; Morales Hernandez, M.E. Role of proteoglycans on skin ageing: A review.
Int. J. Cosmet. Sci. 2020,42, 529–535. [CrossRef]
26.
Park, S.Y.; Byun, E.J.; Lee, J.D.; Kim, S.; Kim, H.S. Air Pollution, Autophagy, and Skin Aging: Impact of Particulate Matter (PM(10))
on Human Dermal Fibroblasts. Int. J. Mol. Sci. 2018,19, 2727. [CrossRef]
27.
Choi, H.; Shin, D.W.; Kim, W.; Doh, S.J.; Lee, S.H.; Noh, M. Asian dust storm particles induce a broad toxicological transcriptional
program in human epidermal keratinocytes. Toxicol. Lett. 2011,200, 92–99. [CrossRef]
28.
Siddens, L.K.; Larkin, A.; Krueger, S.K.; Bradfield, C.A.; Waters, K.M.; Tilton, S.C.; Pereira, C.B.; Lohr, C.V.; Arlt, V.M.; Phillips,
D.H.; et al. Polycyclic aromatic hydrocarbons as skin carcinogens: Comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and
three environmental mixtures in the FVB/N mouse. Toxicol. Appl. Pharmacol. 2012,264, 377–386. [CrossRef] [PubMed]
29.
Qiao, Y.; Li, Q.; Du, H.Y.; Wang, Q.W.; Huang, Y.; Liu, W. Airborne polycyclic aromatic hydrocarbons trigger human skin cells
aging through aryl hydrocarbon receptor. Biochem. Biophys. Res. Commun. 2017,488, 445–452. [CrossRef]
30.
Chiariello, A.M.; Annunziatella, C.; Bianco, S.; Esposito, A.; Nicodemi, M. Polymer physics of chromosome large-scale 3D
organisation. Sci. Rep. 2016,6, 29775. [CrossRef]
31.
Ryu, Y.S.; Kang, K.A.; Piao, M.J.; Ahn, M.J.; Yi, J.M.; Hyun, Y.M.; Kim, S.H.; Ko, M.K.; Park, C.O.; Hyun, J.W. Particulate matter
induces inflammatory cytokine production via activation of NFkappaB by TLR5-NOX4-ROS signaling in human skin keratinocyte
and mouse skin. Redox Biol. 2019,21, 101080. [CrossRef] [PubMed]
32.
Lee, C.W.; Lin, Z.C.; Hsu, L.F.; Fang, J.Y.; Chiang, Y.C.; Tsai, M.H.; Lee, M.H.; Li, S.Y.; Hu, S.C.; Lee, I.T.; et al. Eupafolin ameliorates
COX-2 expression and PGE2 production in particulate pollutants-exposed human keratinocytes through ROS/MAPKs pathways.
J. Ethnopharmacol. 2016,189, 300–309. [CrossRef] [PubMed]
33.
Lin, Z.C.; Lee, C.W.; Tsai, M.H.; Ko, H.H.; Fang, J.Y.; Chiang, Y.C.; Liang, C.J.; Hsu, L.F.; Hu, S.C.; Yen, F.L. Eupafolin nanoparticles
protect HaCaT keratinocytes from particulate matter-induced inflammation and oxidative stress. Int. J. Nanomedicine 2016,11,
3907–3926. [CrossRef] [PubMed]
34.
Lee, S.A.; Jeong, H.; Woo, S.; Hwang, J.Y.; Choi, S.Y.; Kim, S.D.; Choi, M.; Roh, S.; Yu, H.; Hwang, J.; et al. Phase transitions via
selective elemental vacancy engineering in complex oxide thin films. Sci. Rep. 2016,6, 23649. [CrossRef]
35. Schieber, M.; Chandel, N.S. ROS function in redox signaling and oxidative stress. Curr. Biol. 2014,24, R453–R462. [CrossRef]
36.
Ursini, F.; Maiorino, M.; Forman, H.J. Redox homeostasis: The Golden Mean of healthy living. Redox Biol. 2016,8, 205–215.
[CrossRef]
37.
DiStefano, E.; Eiguren-Fernandez, A.; Delfino, R.J.; Sioutas, C.; Froines, J.R.; Cho, A.K. Determination of metal-based hydroxyl
radical generating capacity of ambient and diesel exhaust particles. Inhal. Toxicol. 2009,21, 731–738. [CrossRef]
38.
Shinyashiki, M.; Eiguren-Fernandez, A.; Schmitz, D.A.; Di Stefano, E.; Li, N.; Linak, W.P.; Cho, S.H.; Froines, J.R.; Cho, A.K.
Electrophilic and redox properties of diesel exhaust particles. Environ. Res. 2009,109, 239–244. [CrossRef]
39.
Piao, M.J.; Ahn, M.J.; Kang, K.A.; Ryu, Y.S.; Hyun, Y.J.; Shilnikova, K.; Zhen, A.X.; Jeong, J.W.; Choi, Y.H.; Kang, H.K.; et al.
Particulate matter 2.5 damages skin cells by inducing oxidative stress, subcellular organelle dysfunction, and apoptosis. Arch.
Toxicol. 2018,92, 2077–2091. [CrossRef]
Int. J. Mol. Sci. 2024,25, 9888 15 of 18
40.
Li, N.; Sioutas, C.; Cho, A.; Schmitz, D.; Misra, C.; Sempf, J.; Wang, M.; Oberley, T.; Froines, J.; Nel, A. Ultrafine particulate
pollutants induce oxidative stress and mitochondrial damage. Environ. Health Perspect. 2003,111, 455–460. [CrossRef]
41.
Piao, M.J.; Kang, K.A.; Zhen, A.X.; Fernando, P.; Ahn, M.J.; Koh, Y.S.; Kang, H.K.; Yi, J.M.; Choi, Y.H.; Hyun, J.W. Particulate
Matter 2.5 Mediates Cutaneous Cellular Injury by Inducing Mitochondria-Associated Endoplasmic Reticulum Stress: Protective
Effects of Ginsenoside Rb1. Antioxidants 2019,8, 383. [CrossRef] [PubMed]
42.
Roh, Y.J.; Choi, Y.H.; Shin, S.H.; Lee, M.K.; Won, Y.J.; Lee, J.H.; Cho, B.S.; Park, K.Y.; Seo, S.J. Adipose tissue-derived exosomes
alleviate particulate matter-induced inflammatory response and skin barrier damage in atopic dermatitis-like triple-cell model.
PLoS ONE 2024,19, e0292050. [CrossRef]
43.
Kwack, M.H.; Bang, J.S.; Lee, W.J. Preventative Effects of Antioxidants against PM(10) on Serum IgE Concentration, Mast Cell
Counts, Inflammatory Cytokines, and Keratinocyte Differentiation Markers in DNCB-Induced Atopic Dermatitis Mouse Model.
Antioxidants 2022,11, 1334. [CrossRef] [PubMed]
44.
Niwa, Y.; Sumi, H.; Kawahira, K.; Terashima, T.; Nakamura, T.; Akamatsu, H. Protein oxidative damage in the stratum corneum:
Evidence for a link between environmental oxidants and the changing prevalence and nature of atopic dermatitis in Japan. Br. J.
Dermatol. 2003,149, 248–254. [CrossRef]
45.
Kohen, R.; Nyska, A. Oxidation of biological systems: Oxidative stress phenomena, antioxidants, redox reactions, and methods
for their quantification. Toxicol. Pathol. 2002,30, 620–650. [CrossRef] [PubMed]
46.
Santos, A.G.; da Rocha, G.O.; de Andrade, J.B. Occurrence of the potent mutagens 2- nitrobenzanthrone and 3-nitrobenzanthrone
in fine airborne particles. Sci. Rep. 2019,9, 1. [CrossRef] [PubMed]
47.
Zhen, A.X.; Piao, M.J.; Hyun, Y.J.; Kang, K.A.; Madushan Fernando, P.D.S.; Cho, S.J.; Ahn, M.J.; Hyun, J.W. Diphlorethohydroxy-
carmalol Attenuates Fine Particulate Matter-Induced Subcellular Skin Dysfunction. Mar. Drugs 2019,17, 95. [CrossRef]
48.
Nguyen, L.T.H.; Nguyen, U.T.; Kim, Y.H.; Shin, H.M.; Yang, I.J. Astragali Radix and its compound formononetin ameliorate diesel
particulate matter-induced skin barrier disruption by regulation of keratinocyte proliferation and apoptosis. J. Ethnopharmacol.
2019,228, 132–141. [CrossRef]
49.
Fernando, P.; Piao, M.J.; Zhen, A.X.; Ahn, M.J.; Yi, J.M.; Choi, Y.H.; Hyun, J.W. Extract of Cornus officinalis Protects Keratinocytes
from Particulate Matter-induced Oxidative Stress. Int. J. Med. Sci. 2020,17, 63–70. [CrossRef]
50.
Verdin, A.; Cazier, F.; Fitoussi, R.; Blanchet, N.; Vie, K.; Courcot, D.; Momas, I.; Seta, N.; Achard, S. An
in vitro
model to evaluate
the impact of environmental fine particles (PM(0.3–2.5)) on skin damage. Toxicol. Lett. 2019,305, 94–102. [CrossRef]
51.
Zhu, S.; Li, X.; Dang, B.; Wu, F.; Wang, C.; Lin, C. Lycium Barbarum polysaccharide protects HaCaT cells from PM2.5-induced
apoptosis via inhibiting oxidative stress, ER stress and autophagy. Redox Rep. 2022,27, 32–44. [CrossRef]
52.
Nishitoh, H. CHOP is a multifunctional transcription factor in the ER stress response. J. Biochem. 2012,151, 217–219. [CrossRef]
[PubMed]
53.
Kwon, K.; Park, S.H.; Han, B.S.; Oh, S.W.; Lee, S.E.; Yoo, J.A.; Park, S.J.; Kim, J.; Kim, J.W.; Cho, J.Y.; et al. Negative Cellular Effects
of Urban Particulate Matter on Human Keratinocytes Are Mediated by P38 MAPK and NF-kappaB-dependent Expression of
TRPV 1. Int. J. Mol. Sci. 2018,19, 2660. [CrossRef]
54.
Wang, L.; Lee, W.; Cui, Y.R.; Ahn, G.; Jeon, Y.J. Protective effect of green tea catechin against urban fine dust particle-induced
skin aging by regulation of NF-kappaB, AP-1, and MAPKs signaling pathways. Environ. Pollut. 2019,252, 1318–1324. [CrossRef]
[PubMed]
55.
Liu, T.; Zhang, L.; Joo, D.; Sun, S.C. NF-kappaB signaling in inflammation. Signal Transduct. Target. Ther. 2017,2, 17023. [CrossRef]
56.
Huang, P.H.; Tseng, C.H.; Lin, C.Y.; Lee, C.W.; Yen, F.L. Preparation, characterizations and anti-pollutant activity of 7,3
′
,4
′
-
trihydroxyisoflavone nanoparticles in particulate matter-induced HaCaT keratinocytes. Int. J. Nanomed. 2018,13, 3279–3293.
[CrossRef]
57.
Smith, W.L.; Garavito, R.M.; DeWitt, D.L. Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J. Biol. Chem.
1996,271, 33157–33160. [CrossRef]
58.
O’Neill, L.A.; Bowie, A.G. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat. Rev. Immunol.
2007,7, 353–364. [CrossRef] [PubMed]
59.
Lee, C.W.; Chi, M.C.; Peng, K.T.; Chiang, Y.C.; Hsu, L.F.; Yan, Y.L.; Li, H.Y.; Chen, M.C.; Lee, I.T.; Lai, C.H. Water-Soluble Fullerenol
C(60)(OH)(36) toward Effective Anti-Air Pollution Induced by Urban Particulate Matter in HaCaT Cell. Int. J. Mol. Sci. 2019,20,
4259. [CrossRef]
60.
Dong, L.; Hu, R.; Yang, D.; Zhao, J.; Kan, H.; Tan, J.; Guan, M.; Kang, Z.; Xu, F. Fine Particulate Matter (PM(2.5)) upregulates
expression of Inflammasome NLRP1 via ROS/NF-kappaB signaling in HaCaT Cells. Int. J. Med. Sci. 2020,17, 2200–2206.
[CrossRef]
61.
Gu, X.; Jing, D.; Xiao, Y.; Zhou, G.; Yang, S.; Liu, H.; Chen, X.; Shen, M. Association of air pollution and genetic risks with
incidence of elderly-onset atopic dermatitis: A prospective cohort study. Ecotoxicol. Environ. Saf. 2023,253, 114683. [CrossRef]
[PubMed]
62.
Keller, J.P.; Dunlop, J.H.; Ryder, N.A.; Peng, R.D.; Keet, C.A. Long-Term Ambient Air Pollution and Childhood Eczema in the
United States. Environ. Health Perspect. 2022,130, 57702. [CrossRef] [PubMed]
63.
Park, S.K.; Kim, J.S.; Seo, H.M. Exposure to air pollution and incidence of atopic dermatitis in the general population: A national
population-based retrospective cohort study. J. Am. Acad. Dermatol. 2022,87, 1321–1327. [CrossRef] [PubMed]
Int. J. Mol. Sci. 2024,25, 9888 16 of 18
64.
Ye, C.; Gu, H.; Li, M.; Chen, R.; Xiao, X.; Zou, Y. Air Pollution and Weather Conditions Are Associated with Daily Outpatient
Visits of Atopic Dermatitis in Shanghai, China. Dermatology 2022,238, 939–949. [CrossRef]
65.
Park, T.H.; Park, S.; Cho, M.K.; Kim, S. Associations of particulate matter with atopic dermatitis and chronic inflammatory skin
diseases in South Korea. Clin. Exp. Dermatol. 2022,47, 325–334. [CrossRef]
66.
Wang, H.L.; Sun, J.; Qian, Z.M.; Gong, Y.Q.; Zhong, J.B.; Yang, R.D.; Wan, C.L.; Zhang, S.Q.; Ning, D.F.; Xian, H.; et al. Association
between air pollution and atopic dermatitis in Guangzhou, China: Modification by age and season. Br. J. Dermatol. 2021,184,
1068–1076. [CrossRef] [PubMed]
67.
Bae, Y.J.; Park, K.Y.; Han, H.S.; Kim, Y.S.; Hong, J.Y.; Han, T.Y.; Seo, S.J. Effects of Particulate Matter in a Mouse Model of
Oxazolone-Induced Atopic Dermatitis. Ann. Dermatol. 2020,32, 496–507. [CrossRef]
68.
Tang, K.T.; Ku, K.C.; Chen, D.Y.; Lin, C.H.; Tsuang, B.J.; Chen, Y.H. Adult atopic dermatitis and exposure to air pollutants-a
nationwide population-based study. Ann. Allergy Asthma Immunol. 2017,118, 351–355. [CrossRef]
69.
Kim, Y.M.; Kim, J.; Han, Y.; Jeon, B.H.; Cheong, H.K.; Ahn, K. Short-term effects of weather and air pollution on atopic dermatitis
symptoms in children: A panel study in Korea. PLoS ONE 2017,12, e0175229. [CrossRef]
70.
Liu, W.; Cai, J.; Huang, C.; Hu, Y.; Fu, Q.; Zou, Z.; Sun, C.; Shen, L.; Wang, X.; Pan, J.; et al. Associations of gestational and early
life exposures to ambient air pollution with childhood atopic eczema in Shanghai, China. Sci. Total Environ. 2016,572, 34–42.
[CrossRef]
71.
Wang, I.J.; Tung, T.H.; Tang, C.S.; Zhao, Z.H. Allergens, air pollutants, and childhood allergic diseases. Int. J. Hyg. Environ. Health
2016,219, 66–71. [CrossRef] [PubMed]
72.
Sun, Y.; Meng, Y.; Ou, Z.; Li, Y.; Zhang, M.; Chen, Y.; Zhang, Z.; Chen, X.; Mu, P.; Norback, D.; et al. Indoor microbiome, air
pollutants and asthma, rhinitis and eczema in preschool children—A repeated cross-sectional study. Environ. Int. 2022,161,
107137. [CrossRef] [PubMed]
73.
Huls, A.; Abramson, M.J.; Sugiri, D.; Fuks, K.; Kramer, U.; Krutmann, J.; Schikowski, T. Nonatopic eczema in elderly women:
Effect of air pollution and genes. J. Allergy Clin. Immunol. 2019,143, 378–385.e379. [CrossRef] [PubMed]
74. Wang, X.W.; Tian, Y.H.; Cao, Y.Y.; Song, J.; Li, M.; Wu, Y.; Wang, M.Y.; Huang, Z.; Hu, Y.H. Association between Fine Particulate
Air Pollution and Outpatient Visits for Eczema in Beijing, China: A Time-series Analysis. Biomed. Environ. Sci. 2019,32, 624–627.
[CrossRef]
75.
Li, A.; Fan, L.; Xie, L.; Ren, Y.; Li, L. Associations between air pollution, climate factors and outpatient visits for eczema in
West China Hospital, Chengdu, south-western China: A time series analysis. J. Eur. Acad. Dermatol. Venereol. 2018,32, 486–494.
[CrossRef]
76.
Shah, L.; Mainelis, G.; Ramagopal, M.; Black, K.; Shalat, S.L. Use of a Robotic Sampler (PIPER) for Evaluation of Particulate
Matter Exposure and Eczema in Preschoolers. Int. J. Environ. Res. Public. Health 2016,13, 242. [CrossRef]
77.
Bellinato, F.; Adami, G.; Vaienti, S.; Benini, C.; Gatti, D.; Idolazzi, L.; Fassio, A.; Rossini, M.; Girolomoni, G.; Gisondi, P. Association
Between Short-term Exposure to Environmental Air Pollution and Psoriasis Flare. JAMA Dermatol. 2022,158, 375–381. [CrossRef]
78.
Wu, J.; Chen, H.; Yang, R.; Yu, H.; Shang, S.; Hu, Y. Short-term exposure to ambient fine particulate matter and psoriasis: A
time-series analysis in Beijing, China. Front. Public. Health 2022,10, 1015197. [CrossRef]
79.
Lee, E.H.; Ryu, D.; Hong, N.S.; Kim, J.Y.; Park, K.D.; Lee, W.J.; Lee, S.J.; Kim, S.H.; Do, Y.; Jang, Y.H. Defining the Relationship
between Daily Exposure to Particulate Matter and Hospital Visits by Psoriasis Patients. Ann. Dermatol. 2022,34, 40–45. [CrossRef]
80.
Li, X.; Zhou, L.X.; Yang, L.L.; Huang, X.L.; Wang, N.; Hu, Y.G.; Tang, E.J.; Xiao, H.; Zhou, Y.M.; Li, Y.F.; et al. The relationship
between short-term PM(2.5) exposure and outpatient visits for acne vulgaris in Chongqing, China: A time-series study. Environ.
Sci. Pollut. Res. Int. 2022,29, 61502–61511. [CrossRef]
81.
Li, X.; Cao, Y.; An, S.J.; Xiang, Y.; Huang, H.X.; Xu, B.; Zhang, Y.; Li, Y.F.; Lu, Y.G.; Cai, T.J. The association between short-term
ambient air pollution and acne vulgaris outpatient visits: A hospital-based time-series analysis in Xi’an. Environ. Sci. Pollut. Res.
Int. 2022,29, 14624–14633. [CrossRef] [PubMed]
82.
El Haddad, C.; Gerbaka, N.E.; Hallit, S.; Tabet, C. Association between exposure to ambient air pollution and occurrence of
inflammatory acne in the adult population. BMC Public. Health 2021,21, 1664. [CrossRef] [PubMed]
83.
Liu, W.; Pan, X.; Vierkotter, A.; Guo, Q.; Wang, X.; Wang, Q.; Seite, S.; Moyal, D.; Schikowski, T.; Krutmann, J. A Time-Series
Study of the Effect of Air Pollution on Outpatient Visits for Acne Vulgaris in Beijing. Skin. Pharmacol. Physiol. 2018,31, 107–113.
[CrossRef] [PubMed]
84.
Huang, C.H.; Chen, S.C.; Wang, Y.C.; Wang, C.F.; Hung, C.H.; Lee, S.S. Detrimental correlation between air pollution with skin
aging in Taiwan population. Medicine 2022,101, e29380. [CrossRef]
85.
Peng, F.; Xue, C.H.; Hwang, S.K.; Li, W.H.; Chen, Z.; Zhang, J.Z. Exposure to fine particulate matter associated with senile lentigo
in Chinese women: A cross-sectional study. J. Eur. Acad. Dermatol. Venereol. 2017,31, 355–360. [CrossRef]
86.
Kim, B.E.; Kim, J.; Goleva, E.; Berdyshev, E.; Lee, J.; Vang, K.A.; Lee, U.H.; Han, S.; Leung, S.; Hall, C.F.; et al. Particulate matter
causes skin barrier dysfunction. JCI Insight 2021,6, e145185. [CrossRef]
87.
Woo, Y.R.; Park, S.Y.; Choi, K.; Hong, E.S.; Kim, S.; Kim, H.S. Air Pollution and Atopic Dermatitis (AD): The Impact of Particulate
Matter (PM(10)) on an AD Mouse-Model. Int. J. Mol. Sci. 2020,21, 6079. [CrossRef] [PubMed]
88.
Li, F.; Dong, Y.; Ni, C.; Kan, H.; Yan, S. Fine Particulate Matter (PM2.5) is a Risk Factor for Dermatitis by Promoting the Expression
of Thymic Stromal Lymphopoietin (TSLP) in Keratinocytes. Indian. J. Dermatol. 2020,65, 92–96. [CrossRef]
Int. J. Mol. Sci. 2024,25, 9888 17 of 18
89.
Hidaka, T.; Ogawa, E.; Kobayashi, E.H.; Suzuki, T.; Funayama, R.; Nagashima, T.; Fujimura, T.; Aiba, S.; Nakayama, K.; Okuyama,
R.; et al. The aryl hydrocarbon receptor AhR links atopic dermatitis and air pollution via induction of the neurotrophic factor
artemin. Nat. Immunol. 2017,18, 64–73. [CrossRef]
90.
Sadakane, K.; Ichinose, T.; Takano, H.; Yanagisawa, R.; Inoue, K.; Kawazato, H.; Yasuda, A.; Hayakawa, K. Organic chemicals in
diesel exhaust particles enhance picryl chloride-induced atopic dermatitis in NC/Nga mice. Int. Arch. Allergy Immunol. 2013,162,
7–15. [CrossRef]
91.
Wang, X.; Niu, L.; Kang, A.; Pang, Y.; Zhang, Y.; Wang, W.; Zhang, Y.; Huang, X.; Liu, Q.; Geng, Z.; et al. Effects of ambient PM(2.5)
on development of psoriasiform inflammation through KRT17-dependent activation of AKT/mTOR/HIF-1alpha pathway.
Ecotoxicol. Environ. Saf. 2022,243, 114008. [CrossRef] [PubMed]
92.
Cheng, Z.; Liang, X.; Liang, S.; Yin, N.; Faiola, F. A human embryonic stem cell-based
in vitro
model revealed that ultrafine
carbon particles may cause skin inflammation and psoriasis. J. Environ. Sci. 2020,87, 194–204. [CrossRef]
93.
Kim, H.J.; Bae, I.H.; Son, E.D.; Park, J.; Cha, N.; Na, H.W.; Jung, C.; Go, Y.S.; Kim, D.Y.; Lee, T.R.; et al. Transcriptome analysis of
airborne PM(2.5)-induced detrimental effects on human keratinocytes. Toxicol. Lett. 2017,273, 26–35. [CrossRef]
94.
Noh, H.H.; Shin, S.H.; Roh, Y.J.; Moon, N.J.; Seo, S.J.; Park, K.Y. Particulate matter increases Cutibacterium acnes-induced
inflammation in human epidermal keratinocytes via the TLR4/NF-kappaB pathway. PLoS ONE 2022,17, e0268595. [CrossRef]
[PubMed]
95.
Kwack, M.H.; Ha, D.L.; Lee, W.J. Preventative effects of antioxidants on changes in sebocytes, outer root sheath cells, and
Cutibacterium acnes-pretreated mice by particulate matter: No significant difference among antioxidants. Int. J. Immunopathol.
Pharmacol. 2022,36, 3946320221112433. [CrossRef]
96.
Ahn, Y.; Lee, E.J.; Luo, E.; Choi, J.; Kim, J.Y.; Kim, S.; Kim, S.H.; Bae, Y.J.; Park, S.; Lee, J.; et al. Particulate Matter Promotes
Melanin Production through Endoplasmic Reticulum Stress–Mediated IRE1alpha Signaling. J. Investig. Dermatol. 2022,142,
1425–1434.e1426. [CrossRef]
97.
Moon, I.J.; Kim, W.; Kim, S.Y.; Lee, J.; Yoo, H.; Bang, S.; Song, Y.; Chang, S.E. Saponins of Korean Red Ginseng May Protect
Human Skin from Adipokine-Associated Inflammation and Pigmentation Resulting from Particulate Matter Exposure. Nutrients
2022,14, 845. [CrossRef] [PubMed]
98.
Ko, H.J.; Kim, J.H.; Lee, G.S.; Shin, T. Sulforaphane controls the release of paracrine factors by keratinocytes and thus miti-
gates particulate matter-induced premature skin aging by suppressing melanogenesis and maintaining collagen homeostasis.
Phytomedicine 2020,77, 153276. [CrossRef]
99.
Kim, M.; Kim, J.H.; Jeong, G.J.; Park, K.Y.; Lee, M.K.; Seo, S.J. Particulate matter induces pro-inflammatory cytokines via
phosphorylation of p38 MAPK possibly leading to dermal inflammaging. Exp. Dermatol. 2019,28, 809–815. [CrossRef]
100.
Kim, B.E.; Leung, D.Y.M. Significance of Skin Barrier Dysfunction in Atopic Dermatitis. Allergy Asthma Immunol. Res. 2018,10,
207–215. [CrossRef]
101. Weidinger, S.; Novak, N. Atopic dermatitis. Lancet 2016,387, 1109–1122. [CrossRef]
102.
Baek, J.O.; Cho, J.; Roh, J.Y. Associations between ambient air pollution and medical care visits for atopic dermatitis. Environ. Res.
2021,195, 110153. [CrossRef] [PubMed]
103.
Pareek, A.; Kumari, L.; Pareek, A.; Chaudhary, S.; Ratan, Y.; Janmeda, P.; Chuturgoon, S.; Chuturgoon, A. Unraveling Atopic
Dermatitis: Insights into Pathophysiology, Therapeutic Advances, and Future Perspectives. Cells 2024,13, 425. [CrossRef]
[PubMed]
104.
Fadadu, R.P.; Green, M.; Grimes, B.; Jewell, N.P.; Seth, D.; Vargo, J.; Wei, M.L. Association of Wildfire Air Pollution With Clinic
Visits for Psoriasis. JAMA Netw. Open 2023,6, e2251553. [CrossRef] [PubMed]
105.
Greb, J.E.; Goldminz, A.M.; Elder, J.T.; Lebwohl, M.G.; Gladman, D.D.; Wu, J.J.; Mehta, N.N.; Finlay, A.Y.; Gottlieb, A.B. Psoriasis.
Nat. Rev. Dis. Primers 2016,2, 16082. [CrossRef] [PubMed]
106.
Armstrong, A.W.; Read, C. Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review. JAMA 2020,323,
1945–1960. [CrossRef]
107. Ni, X.; Lai, Y. Keratinocyte: A trigger or an executor of psoriasis? J. Leukoc. Biol. 2020,108, 485–491. [CrossRef]
108.
Christmann, C.; Zenker, S.; Martens, L.; Hubner, J.; Loser, K.; Vogl, T.; Roth, J. Interleukin 17 Promotes Expression of Alarmins
S100A8 and S100A9 During the Inflammatory Response of Keratinocytes. Front. Immunol. 2020,11, 599947. [CrossRef]
109.
D’Amico, F.; Skarmoutsou, E.; Granata, M.; Trovato, C.; Rossi, G.A.; Mazzarino, M.C. S100A7: A rAMPing up AMP molecule in
psoriasis. Cytokine Growth Factor. Rev. 2016,32, 97–104. [CrossRef]
110. Williams, H.C.; Dellavalle, R.P.; Garner, S. Acne vulgaris. Lancet 2012,379, 361–372. [CrossRef]
111.
Perry, A.; Lambert, P. Propionibacterium acnes: Infection beyond the skin. Expert. Rev. Anti Infect. Ther. 2011,9, 1149–1156.
[CrossRef] [PubMed]
112.
Kurokawa, I.; Danby, F.W.; Ju, Q.; Wang, X.; Xiang, L.F.; Xia, L.; Chen, W.; Nagy, I.; Picardo, M.; Suh, D.H.; et al. New developments
in our understanding of acne pathogenesis and treatment. Exp. Dermatol. 2009,18, 821–832. [CrossRef]
113.
Shin, J.W.; Kwon, S.H.; Choi, J.Y.; Na, J.I.; Huh, C.H.; Choi, H.R.; Park, K.C. Molecular Mechanisms of Dermal Aging and
Antiaging Approaches. Int. J. Mol. Sci. 2019,20, 2126. [CrossRef] [PubMed]
114.
Fisher, G.J.; Varani, J.; Voorhees, J.J. Looking older: Fibroblast collapse and therapeutic implications. Arch. Dermatol. 2008,144,
666–672. [CrossRef]
Int. J. Mol. Sci. 2024,25, 9888 18 of 18
115.
Quan, T.; Fisher, G.J. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin
Aging: A Mini-Review. Gerontology 2015,61, 427–434. [CrossRef] [PubMed]
116.
Berneburg, M.; Plettenberg, H.; Krutmann, J. Photoaging of human skin. Photodermatol. Photoimmunol. Photomed. 2000,16, 239–244.
[CrossRef] [PubMed]
117.
Misra, N.; Clavaud, C.; Guinot, F.; Bourokba, N.; Nouveau, S.; Mezzache, S.; Palazzi, P.; Appenzeller, B.M.R.; Tenenhaus, A.;
Leung, M.H.Y.; et al. Multi-omics analysis to decipher the molecular link between chronic exposure to pollution and human skin
dysfunction. Sci. Rep. 2021,11, 18302. [CrossRef]
118.
Lehtimaki, J.; Karkman, A.; Laatikainen, T.; Paalanen, L.; von Hertzen, L.; Haahtela, T.; Hanski, I.; Ruokolainen, L. Patterns in the
skin microbiota differ in children and teenagers between rural and urban environments. Sci. Rep. 2017,7, 45651. [CrossRef]
119.
Yan, D.; Li, M.; Si, W.; Ni, S.; Liu, X.; Chang, Y.; Guo, X.; Wang, J.; Bai, J.; Chen, Y.; et al. Haze Exposure Changes the Skin Fungal
Community and Promotes the Growth of Talaromyces Strains. Microbiol. Spectr. 2023,11, e0118822. [CrossRef]
120.
Zeldin, J.; Chaudhary, P.P.; Spathies, J.; Yadav, M.; D’Souza, B.N.; Alishahedani, M.E.; Gough, P.; Matriz, J.; Ghio, A.J.; Li, Y.; et al.
Exposure to isocyanates predicts atopic dermatitis prevalence and disrupts therapeutic pathways in commensal bacteria. Sci. Adv.
2023,9, eade8898. [CrossRef]
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