Functions of the aryl hydrocarbon receptor in the skin

Esser, Charlotte; Bargen, Imke; Weighardt, Heike; Haarmann‐Stemmann, Thomas; Krutmann, Jean

doi:10.1007/s00281-013-0394-4

Cited by 159 publications

(174 citation statements)

References 134 publications

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“…Furthermore, AhR-ROS-dependent regulation of IL-8 in normal human epidermal keratinocytes [60] and IL-6 in human sebocytes [61] by BaP provides a plausible explanation, at least in part, for why cigarette smoking exacerbates IL-8-related skin diseases such as psoriasis, palmoplantar pustulosis, and acne. In addition, the AhR signal pathway-induced Th17 differentiation and secretion of IL-17 and IL-22 as well as the interaction with estrogen may relate to the autoimmune skin diseases SLE and tuberous sclerosis [62][63][64], but the clinical correlation between them and EDCs is still uncertain.…”

Section: Inflammatory and Allergic Skin Diseasesmentioning

confidence: 99%

Endocrine-disrupting chemicals and skin manifestations

Qiang

Zouboulis

2016

Rev Endocr Metab Disord

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Endocrine-disrupting chemicals (EDCs) are exogenous compounds that have the ability to disrupt the production and actions of hormones through direct or indirect interaction with hormone receptors, thus acting as agonists or antagonists. Human health is affected after either individual occupation or dietary and environmental exposure to EDCs. On the other hand, skin is one of the largest organs of the body and its main function is protection from noxious substances. EDCs perturb the endocrine system, and they are also carcinogenic, immunotoxic, and hepatotoxic to human skin. In addition, their effects on keratinocytes, melanocytes, sebocytes, inflammatory and immunological cells, and skin stem cells produce inflammatory and allergic skin diseases, chloracne, disorders of skin pigmentation, skin cancer, and skin aging. Mechanisms, which EDCs use to induce these skin disorders are complicated, and involve the interference of endogenous hormones and most importantly the activation of the aryl hydrocarbon receptor signal pathway. Further studies on EDCs and skin diseases are necessary to elucidate these mechanisms.

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Section: Inflammatory and Allergic Skin Diseasesmentioning

confidence: 99%

Endocrine-disrupting chemicals and skin manifestations

Qiang

Zouboulis

2016

Rev Endocr Metab Disord

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“…AhR is activated for example by environmental pollutants, mainly dioxins and PAHs, and takes part in the biochemical signaling cascade and toxic effects of these pollutants. It is also involved in processes such as cell growth, proliferation, and differentiation [13,30]. Tauchi et al (2005) showed that activation of the AhR in keratinocytes in transgenic mice caused inflammatory skin lesions and immunological imbalance, revealed as skin rashes and itches similar to those observed during atopic dermatitis [32].…”

Section: Activation Of the Aryl Hydrocarbon Receptor (Ahr)mentioning

confidence: 99%

“…AhR is a ligand activated receptor, which is expressed in all types of cells in the skin and other tissues which are in contact with environmental factors, such as lungs or liver [30]. Its function is to support a cellular response for exogenous signals by regulation of cell homeostasis, activation of immune cells, and induction of xenobiotic metabolizing enzymes [30,31].…”

Section: Activation Of the Aryl Hydrocarbon Receptor (Ahr)mentioning

confidence: 99%

“…Its function is to support a cellular response for exogenous signals by regulation of cell homeostasis, activation of immune cells, and induction of xenobiotic metabolizing enzymes [30,31]. AhR is activated for example by environmental pollutants, mainly dioxins and PAHs, and takes part in the biochemical signaling cascade and toxic effects of these pollutants.…”

Section: Activation Of the Aryl Hydrocarbon Receptor (Ahr)mentioning

confidence: 99%

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The Impact of Pollution on Skin and Proper Efficacy Testing for Anti-Pollution Claims

et al. 2018

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Exposure to pollution can cause oxidative stress, premature ageing, inflammation, and diseases. Since most of us are exposed to pollution, protection is important. This can be achieved through skin protection or through protection with respect to food and food supplements. There is a wide range of products on the market with anti-pollution claims. However, it is important that these claims are thoroughly validated by proper efficacy testing. When skin cells are exposed to pollution factors, changes in a number of skin properties can be observed, such as lipid composition, lipid and protein oxidation, pH, sebum secretion rate, oxidative stress, inflammation markers, and collagen and elastin levels. These can be measured and used as markers to verify anti-pollution claims. In the present review, we summarize some of the most important in vitro and in vivo tests that are used to determine if an ingredient or formulation has anti-pollution efficacy.

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“…AHR activity promotes their expansion and is obligatory for IL-22 production. AHR also encourages IL21 and IL23 output and inhibitory effects on Th17 [19]. The skin has several subsets of IL-17 producing cells.…”

Section: Introductionmentioning

confidence: 99%

Metadichol, A Novel ROR Gamma Inverse Agonist and Its Applications in Psoriasis

PR¹

2017

J Clin Exp Dermatol Res

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Psoriasis affects 3% of the population worldwide, and there is no known cure. Psoriasis is associated with an increased risk of psoriatic arthritis, lymphomas, cardiovascular disease, and Crohn's disease. Psoriasis treatments today include steroid and vitamin D3 cream, ultraviolet light, and immune systemsuppressing medications such as methotrexate.The T cells responsible for psoriasis are Th1 and Th l7 cells. IL-22, produced by Th17 cells, is crucial for the proliferation of keratinocytes. IL-22 with the help of IL-17 can induce the critical events of psoriasis. To maintain Th17 cells, IL-23 is required, and it is released from tumor necrosis factor-alpha (TNF-alpha) induced pathways. The pathophysiology of psoriasis involves RORC (retinoic acid receptor-related orphan nuclear receptor gamma) as a critical transcription factor for the development of Th17 cells. FDA has approved an antibody Secukinumab ® targeting TNF-α for the treatment of psoriasis. Other FDA approved drugs are Tremfya ® targeting IL23 for treatment of moderate to severe plaque psoriasis and Taltz ® that blocks IL17 for treatment of plaque psoriasis.Metadichol ® a nanoformulation of long-chain lipid alcohols derived from food is a TNF-alpha inhibitor and also binds to Vitamin D receptor (VDR) that could have beneficial effects on Psoriasis. VDR modulates Th1-mediated inflammatory disease like psoriasis. We now present evidence that Metadichol is an inverse agonist of RORγt and AHR (Aryl Hydrocarbon Receptor) thus controlling Th17, IL17 and IL22. Being a TNF-alpha inhibitor, it can control IL23 thus blocking the significant pathways that exacerbate psoriasis. We present case studies of 7 patients afflicted with psoriasis and skin related conditions and how treatment with Metadichol resolved the underlying disease. Metadichol ® has properties that allow its use as a safe nontoxic, toxic solution to combating the growing number of psoriasis cases. TNF-a is implicated in the pathogenesis of multiple inflammatory and autoimmune conditions such as like Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, and psoriasis. The development of TNF-α inhibitors has improved therapeutic options for patients with these conditions. However, TNF-α inhibitors are paradoxically inducing the new onset of psoriasis or worsening preexisting quiescent psoriatic diseases [13].Genomic effects of 1, 25(OH)2D3 are controlled via binding to a nuclear receptor protein, VDR (vitamin D receptor). VDR is expressed in keratinocytes, fibroblasts, Langerhans cells, sebaceous gland cells, endothelial cells and almost the entire cell types related to the skin immune system [14]. Vitamin D and analogs display in the skin effects on cellular differentiation, proliferation, regulate psoriasis and represent a standard therapy. However, there is a need for highly antiproliferative or anti-inflammatory acting vitamin D analogs that exhibit only minor calcemic activity. Selective vitamin D signaling pathways that exert little calcemic activity would...

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Functions of the aryl hydrocarbon receptor in the skin

Cited by 159 publications

References 134 publications

Endocrine-disrupting chemicals and skin manifestations

Endocrine-disrupting chemicals and skin manifestations

The Impact of Pollution on Skin and Proper Efficacy Testing for Anti-Pollution Claims

Metadichol, A Novel ROR Gamma Inverse Agonist and Its Applications in Psoriasis

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