Attila Oláh

University of Debrecen · Department of Physiology

We have recently shown that fluoxetine (FX) suppressed polyinosinic-polycytidylic acid-induced inflammatory response and endothelin release in human epidermal keratinocytes, via the indirect inhibition of the phosphoinositide 3-kinase (PI3K)-pathway. Because PI3K-signaling is a positive regulator of the proliferation, in the current, highly focused...

Fluoxetine is a safe antidepressant with remarkable anti‐inflammatory actions; therefore, we aimed to investigate its effects on immortalized (HaCaT) as well as primary human epidermal keratinocytes in a polyinosinic‐polycytidylic acid (p(I:C))‐induced inflammatory model. We found that a non‐cytotoxic concentration (MTT‐assay, CyQUANT‐assay) of flu...

Cannabidiol (CBD) and (−)-cannabigerol (CBG) are two major non-psychotropic phytocannabinoids that have many beneficial biological properties. However, due to their low water solubility and prominent first-pass metabolism, their oral bioavailability is moderate, which is unfavorable for medicinal use. Therefore, there is a great need for appropriat...

Introduction Extracts and compounds isolated from hemp (Cannabis sativa) are increasingly gaining popularity in the treatment of a number of diseases, with topical formulations for dermatological conditions leading the way. Phytocannabinoids such as ( )-cannabidiol, ( )-cannabinol and ( )-Δ9-tetrahydrocannabivarin (CBD, CBN, and THCV, respectively)...

(‑)-Cannabidiol (CBD) and (‑)-cannabigerol (CBG) are two major non-psychotropic phytocannabinoids that have many beneficial biological properties. However, due to their low water solubility and prominent first-pass metabolism, their oral bioavailability is moderate, which is unfavorable for medicinal use. Therefore, there is a great need for approp...

Langerhans cells (LCs) are the sole professional antigen-presenting cell normally found in the human epidermal compartment. Research into their physiological role is hindered by the fact that they are invariably activated during isolation from the skin. To overcome this challenge, we turned to a monocyte-derived LC model (moLC), which we characteri...

This review presents several aspects of the innovative concept of sebaceous immunobiology, which summarizes the numerous activities of the sebaceous gland including its classical physiological and pathophysiological tasks, namely sebum production and the development of seborrhea and acne. Sebaceous lipids, which represent 90% of the skin surface li...

Atopic dermatitis (AD) is one of the most common skin diseases, the prevalence of which is especially high among children. Although our understanding about its pathogenesis has substantially grown in recent years, and hence, several novel therapeutic targets have been successfully exploited in the management of the disease, we still lack curative t...

Pruritus or itch generated in the skin is one of the most widespread symptoms associated with various dermatological and systemic (immunological) conditions. Although many details about the molecular mechanisms of the development of both acute and chronic itch were uncovered in the last 2 decades, our understanding is still incomplete and the clini...

Photodamage-induced and viral keratitis could benefit from treatment with novel nonsteroid anti-inflammatory agents. Therefore, we determined whether human corneal epithelial cells (HCECs) express members of the endocannabinoid system (ECS), and examined how the endocannabinoid anandamide (AEA, N-arachidonoyl ethanolamine) influences the Toll-like...

Adipokines are the primary mediators of adipose tissue-induced and regulated systemic inflammatory diseases; however, recent findings revealed that serum levels of various adipokines correlate also with the onset and the severity of dermatological diseases. Importantly, further data confirmed that the skin serves not only as a target for adipokine...

During the molecular transduction of itch, the stimulation of pruriceptors on sensory fibers leads to the activation or sensitization of ion channels, which results in a consequent depolarization of the neurons. These ion channels mostly belong to the transient receptor potential (TRP) channels, which are involved in nociception and thermosensation...

Epidermal energy metabolism is relevant to skin physiology, aging, and photodamage. While selected hormones stimulate epidermal keratinocyte mitochondrial activity, its negative regulation remains unknown. In several cell types, cannabinoid receptor 1 (CB1) is expressed both in the cell membrane (cmCB1), and in the mitochondrial outer membrane (mtC...

We have shown previously that endocannabinoids promote sebaceous lipogenesis, and sebocytes are involved in the metabolism of the endocannabinoid-like substance oleoylethanolamide (OEA). OEA is an endogenous activator of GPR119, a recently deorphanized receptor, which currently is being investigated as a promising antidiabetic drug target. In this...

Background: Volatile anaesthetics (VAs) are the most widely used compounds to induce reversible loss of consciousness and maintain general anaesthesia during surgical interventions. Although the mechanism of their action is not yet fully understood, it is generally believed, that VAs depress central nervous system functions mainly through modulati...

Nicotinic acid (NA) activates hydroxycarboxylic acid receptor 2 (HCA2), and it is widely used in treating dyslipidaemias. Since its side effects include skin dryness, whereas its deficiency can be accompanied by dyssebacia, characterized by sebaceous gland enlargement, we asked if HCA2 is expressed on human sebocytes, and if NA influences sebocyte...

The endocannabinoid system (ECS) has lately been proven to be an important, multifaceted homeostatic regulator, which influences a wide-variety of physiological processes all over the body. Its members, the endocannabinoids (eCBs; e.g., anandamide), the eCB-responsive receptors (e.g., CB1, CB2), as well as the complex enzyme and transporter apparat...

Regulation of pH is one of the most complex mechanisms in human physiology. Indeed, the H+ ion concentration not only contributes to the establishment and maintenance of the body's homeostasis (by defining isohydria) but it also acts as an ionic, electric or osmotic driving force; provides optimum conditions for the proper functions of a plethora o...

Polyols (e.g. glycerol, xylitol) are implicated as moisturizers of the skin and other epithelial tissues. However, we lack information about their exact cellular mechanisms and their effects on the gene expression profiles. Therefore, in this study, we aimed at investigating the effects of glycerol and xylitol on human epidermal keratinocytes. The...

We have previously shown that i) endocannabinoids (eCB; e.g. anandamide [AEA]) are involved in the maintenance of homeostatic sebaceous lipid production (SLP) in human sebaceous glands (SG); and ii) eCB treatment dramatically increases SLP. Here, we aimed to investigate the expression of the major eCB synthesizing and degrading enzymes, and to stud...

It is well known that certain active ingredients of the plants of Cannabis genus, i.e., the “phytocannabinoids” [pCBs; e.g., (−)-trans-Δ⁹-tetrahydrocannabinol (THC), (−)-cannabidiol, etc.] can influence a wide array of biological processes, and the human body is able to produce endogenous analogs of these substances [“endocannabinoids” (eCB), e.g.,...

The sebaceous gland, long considered an evolutionary relic with little-to-no physiological relevance in humans, has emerged in recent decades as a key orchestrator and contributor to many cutaneous functions. In addition to the classical physico-chemical barrier function of the skin against constant environmental challenges, a more novel, neuro-imm...

Background: Atopic eczema (AE) is a chronic inflammatory and pruritic skin disease. There is still an unmet need for topical anti-inflammatory and anti-pruritic substances exhibiting an excellent safety profile. The endocannabinoid system is known to regulate various aspects of cutaneous barrier and immune functions, thus targeting it may be a val...

Acne is a common skin disease characterized by elevated sebum production and inflammation of the sebaceous glands. We have previously shown that a non-psychotropic phytocannabinoid ((–)-cannabidiol [CBD]) exerted complex anti-acne effects by normalizing ‘pro-acne agents’-induced excessive sebaceous lipid production, reducing proliferation and allev...

Echinacea purpurea extracts (purple coneflower) are known to have immunemodulatory effects. Several alkamides, as the major lipophilic constituents, bind to cannabinoid receptors 1 and 2. Since the endocannabinoid system is of importance in inflammatory skin diseases, anti-inflammatory activity of alkamides was investigated. Therefore the new lipophil...

Data S1 Supplementary materials and methods and Supplementary Figures S1‐S3.

In addition to producing sebum, sebocytes link lipid metabolism with inflammation at a cellular level and hence, greatly resemble adipocytes. However, so far no analysis was performed to identify and characterize the adipocyte-associated inflammatory proteins, the members of the adipokine family in sebocytes. Therefore, we determined the expression...

Transient receptor potential canonical-6 (TRPC6) ion channels, expressed at high levels in podocytes of the filtration barrier, are recently implicated in the pathogenesis of various forms of proteinuric kidney diseases. Indeed, inherited or acquired up-regulation of TRPC6 activities are suggested to play a role in podocytopathies. Yet, we possess...

Unwanted hair growth and loss affect quality of life of millions world-wide; therefore better understanding of the (patho)physiology of human hair follicles (HFs), and thereby identification of novel therapeutic approaches, are important fields of experimental dermatology. Human hair follicles (HFs) express thyroid hormone receptors (TRs) and respond...

Human hair follicles (HFs) express thyroid hormone receptors (TRs) and respond to their stimulation, both in vivo and in vitro. We have previously shown that thyroid hormones (THs) are potent regulators of human HFs biology. For example, thyroxine prolongs the growth phase of the hair cycle (anagen), and stimulates HF pigmentation and mitochondrial...

The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic ag...

Echinacea purpurea extracts (purple coneflower) are known to have immunomodulatory effects. Several alkamides, major lipophilic constituents, bind to cannabinoid receptors 1 and 2 (CB1-R and CB2-R). N-Isobutyl dodeca-2E,4E-diene amide (15) binds to CB2-R (Ki = 60 nM) and CB1-R (Ki = 1.94 μM). Since the endocannabinoid system is of importance in inf...

Emerging evidence suggests that transient receptor potential ( TRP ) ion channels not only act as ‘polymodal cellular sensors’ on sensory neurons but are also functionally expressed by a multitude of non‐neuronal cell types. This is especially true in the skin, one of the largest organs of the body, where they appear to be critically involved in re...

An increasing body of evidence argues for that endocannabinoids (eCBs) play an essential role in the regulation of the skin immune system, and that the elevation of the cutaneous eCB tone, by the inhibition of the eCB degrading enzyme fatty acid amide hydrolase (FAAH), results in anti-inflammatory effects. Therefore, in the current study, we aimed...

Our goal was to investigate the effect of heat shock on human monocyte-derived dendritic cells (DCs) and to dissect the role of thermosensitive transient receptor potential (TRP) in the process. We provide evidence that a short heat shock challenge (43°C) decreased the endocytotic activity of the DCs and that this effect could be alleviated by the...

During embryonic development, the skin, the largest organ of the human body, and nervous system are both derived from the neuroectoderm. Consequently, several key factors and mechanisms that influence and control central or peripheral nervous system activities are also present and hence involved in various regulatory mechanisms of the skin. Apparen...

Protein kinase C (PKC) isoforms have crucial roles in cutaneous signaling. Interestingly, we lack information about their involvement in human sebaceous gland biology. Therefore, in this current study, we investigated the functions of the PKC system in human immortalized SZ95 sebocytes. Using molecular biological approaches, imaging, and functional...

In the current study, we aimed at identifying the functional role of transient receptor potential vanilloid-3 (TRPV3) ion channel in the regulation of human hair growth. Using human organ-cultured hair follicles (HFs) and cultures of human outer root sheath (ORS) keratinocytes, we provide the first evidence that activation of TRPV3 inhibits human h...

The pilosebaceous unit of the human skin consists of the hair follicle and the sebaceous gland. Within this "mini-organ", the sebaceous gland has been neglected by the researchers of the field for several decades. Actually, it was labeled as a reminiscence of human development ("a living fossil with a past but no future"), and was thought to solely...

We have recently shown that lipid mediators of the emerging endocannabinoid system (ECS) are key players of growth control of the human pilosebaceous unit. In this study, we asked whether the prototypic endocannabinoid anandamide (N-arachidonoylethanolamine, AEA) has a role in growth and survival of epidermal keratinocytes (KCs). Using human cultur...