Hong SP, Kim MJ, Jung MY, Jeon H, Goo J, Ahn SK et al.Biopositive effects of low-dose UVB on epidermis: coordinate upregulation of antimicrobial peptides and permeability barrier reinforcement. J Invest Dermatol 128:2880-2887
Whereas high-dose ultraviolet B (UVB) is detrimental to the epidermal permeability barrier, suberythemal doses of UVB are used to treat atopic dermatitis (AD), which is characterized by defective permeability barrier and antimicrobial function. As epidermal permeability barrier and antimicrobial peptide (AMP) expression are coregulated and interdependent functions, we hypothesized that suberythemal doses of UVB exposure could regulate AMP expression in parallel with permeability barrier function. Hairless mice were exposed to 40 mJ cm(-2) UVB (about 1/2 minimal erythema dose) daily for 1 or 3 days. Twenty-four hours after the last exposure, epidermal barrier function was assessed and skin specimens were taken for western blotting, immunohistochemistry, and quantitative reverse transcription-PCR for mouse beta-defensin (mBD)-2, mBD3 and cathelin-related antimicrobial peptide (CRAMP). mRNA levels of the vitamin D receptor (VDR), 1alpha-hydroxylase and key epidermal lipid synthetic enzymes were also quantified. After 3 days of UVB exposure, acceleration of barrier recovery and augmentation in expression of epidermal differentiation markers (for example, involucrin and filaggrin) occurred in parallel with increased mBD2, mBD3, and CRAMP expression at both the mRNA and protein level. VDR, 1alpha-hydroxylase, and the major epidermal lipid synthetic enzymes were also upregulated. When an inhibitor of 1alpha, 25 dihydroxyvitamin D(3) formation, ketoconazole, was applied immediately after UVB exposure, the cutaneous vitamin D system was inhibited, which in turn blocked epidermal lipid synthesis, AMP expression, and permeability barrier homeostasis, suggesting that the beneficial effect of low-dose UVB depends, at least in part, on activation of the cutaneous vitamin D system. Our results provide new insights into the mechanisms whereby low-dose UVB comprises effective therapy for AD.
"The mechanism of action in AD has not been elucidated; however, the proper UV dose has positive effects on the epidermal permeability barrier function by immunomodulating apoptosis of inflammatory cells, reducing the number of cutaneous nerve fibers, inhibiting the Langerhans cells and altering cytokine production.67 In addition, a suberythemal dose of UVB on the skin exerts beneficial effects on the SC barrier function by activating the cutaneous vitamin D system.68,69 In addition, UV initiates endoplasmic reticulum (ER) stress responses including downstream activation of the transcription factor, NF-κB.70 "
[Show abstract][Hide abstract] ABSTRACT: Atopic dermatitis (AD) is a multifactorial inflammatory skin disease perpetuated by gene-environmental interactions and which is characterized by genetic barrier defects and allergic inflammation. Recent studies demonstrate an important role for the epidermal permeability barrier in AD that is closely related to chronic immune activation in the skin during systemic allergic reactions. Moreover, acquired stressors (e.g., Staphylococcus aureus infection) to the skin barrier may also initiate inflammation in AD. Many studies involving patients with AD revealed that defective skin barriers combined with abnormal immune responses might contribute to the pathophysiology of AD, supporting the outside-inside hypothesis. In this review, we discuss the recent advances in human and animal models, focusing on the defects of the epidermal permeability barrier, its immunologic role and barrier repair therapy in AD.
"A study on hairless mice exposed to 0.5 × MED UVB irradiation (40 mJ/cm2) daily for 14 days demonstrated a significant reduction in the levels of covalently bound Cer and disrupted multilamellar structures (39). By contrast, a separate study concerning hairless mice irradiated with the same dose of UVB daily for 3 days demonstrated no clinically evident inflammation or barrier disruption (68). A dose of 0.5 × MED UVB irradiation for 3 days, prior to tape-stripping, resulted in significantly accelerated barrier recovery rates, implying that repeated, short-term exposure to low-dose UVB significantly accelerates the kinetics of barrier recovery following acute insults (68). "
[Show abstract][Hide abstract] ABSTRACT: Exposure of the skin to ultraviolet (UV) radiation induces various harmful effects in the tissues, particularly disruption of the epidermal barrier. However, ultraviolet B (UVB) irradiation has been applied in the treatment of atopic dermatitis, a skin disease in which the epidermal barrier is defective. We reviewed the homeostasis of the epidermal barrier and several studies investigating the adverse and beneficial effects caused by different doses of UVB irradiation in the epidermal barrier. It may be concluded that, despite the harmful effects of UVB irradiation on the skin, UVB irradiation is able to exert beneficial effects in the epidermal barrier when administered in suberythemal doses and over a relatively short period of time, with no clinically evident inflammation or barrier disruption. This may be a useful therapeutic strategy for the use of UVB irradiation in the treatment of skin diseases with a disrupted epidermal barrier, such as atopic dermatitis, while reducing or avoiding the side-effects.
Experimental and therapeutic medicine 08/2013; 6(2):287-292. DOI:10.3892/etm.2013.1175 · 1.27 Impact Factor
"In experiments with mice, Hong et al. (2008) observed a faster recovery
of the skin barrier in the group treated with narrowband UVB phototherapy, observing
higher histological levels of filaggrin and involucrin in this population. Phototherapy-induced vitamin D was considered responsible for accelerating the epidermal
barrier recovery.66 "
[Show abstract][Hide abstract] ABSTRACT: Patients with atopic dermatitis have genetically determined risk factors that affect the barrier function of the skin and immune responses that interact with environmental factors. Clinically, this results in an intensely pruriginous and inflamed skin that allows the penetration of irritants and allergens and predisposes patients to colonization and infection by microorganisms. Among the various etiological factors responsible for the increased prevalence of atopic diseases over the past few decades, the role of vitamin D has been emphasized. As the pathogenesis of AD involves a complex interplay of epidermal barrier dysfunction and dysregulated immune response, and vitamin D is involved in both processes, it is reasonable to expect that vitamin D's status could be associated with atopic dermatitis' risk or severity. Such association is suggested by epidemiological and experimental data. In this review, we will discuss the evidence for and against this controversial relationship, emphasizing the possible etiopathogenic mechanisms involved.
Jorien van der Schaft, Ron H N van Schaik, Arjan D van Zuilen, Dirk-Jan Hijnen, Maarten Ten Berg, Marcel P H van den Broek, Carla A F M Bruijnzeel-Koomen, Marjolein S de Bruin-Weller
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