scholarly journals Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis

2019 ◽  
Vol 20 (21) ◽  
pp. 5424 ◽  
Author(s):  
Masutaka Furue ◽  
Akiko Hashimoto-Hachiya ◽  
Gaku Tsuji
Keyword(s):  
Oxidative Stress ◽  
Atopic Dermatitis ◽  
Aryl Hydrocarbon Receptor ◽  
T Regulatory Cells ◽  
Skin Barrier ◽  
Related Factor ◽  
T Helper 17 ◽  
Aryl Hydrocarbon ◽  
Sensitive Sensor ◽  
Tryptophan Photoproducts

The aryl hydrocarbon receptor (AHR)/AHR-nuclear translocator (ARNT) system is a sensitive sensor for small molecular, xenobiotic chemicals of exogenous and endogenous origin, including dioxins, phytochemicals, microbial bioproducts, and tryptophan photoproducts. AHR/ARNT are abundantly expressed in the skin. Once activated, the AHR/ARNT axis strengthens skin barrier functions and accelerates epidermal terminal differentiation by upregulating filaggrin expression. In addition, AHR activation induces oxidative stress. However, some AHR ligands simultaneously activate the nuclear factor-erythroid 2-related factor-2 (NRF2) transcription factor, which is a master switch of antioxidative enzymes that neutralizes oxidative stress. The immunoregulatory system governing T-helper 17/22 (Th17/22) and T regulatory cells (Treg) is also regulated by the AHR system. Notably, AHR agonists, such as tapinarof, are currently used as therapeutic agents in psoriasis and atopic dermatitis. In this review, we summarize recent topics on AHR related to atopic dermatitis and psoriasis.

scholarly journals IL-24 Negatively Regulates Keratinocyte Differentiation Induced by Tapinarof, an Aryl Hydrocarbon Receptor Modulator: Implication in the Treatment of Atopic Dermatitis

2020 ◽  
Vol 21 (24) ◽  
pp. 9412
Author(s):  
Yen Hai Vu ◽  
Akiko Hashimoto-Hachiya ◽  
Masaki Takemura ◽  
Ayako Yumine ◽  
Yasutaka Mitamura ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Aryl Hydrocarbon Receptor ◽  
Skin Barrier ◽  
Janus Kinase ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Dependent Manner ◽  
Jak Inhibitors ◽  
Barrier Dysfunction ◽  
Aryl Hydrocarbon

Skin barrier dysfunction, including reduced filaggrin (FLG) and loricrin (LOR) expression, plays a critical role in atopic dermatitis (AD) development. Since aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, mediates keratinocyte differentiation, it is a potential target for AD treatment. Recently, clinical studies have shown that tapinarof, an AHR modulator, attenuated the development of AD. To examine the molecular mechanism involved in this, we analyzed tapinarof-treated normal human epidermal keratinocytes (NHEKs). Tapinarof upregulated FLG and LOR mRNA and protein expression in an AHR-dependent manner. Tapinarof also induced the secretion of IL-24, a cytokine that activates Janus kinase (JAK)-signal transducer and activator of transcription (STAT), leading to the downregulation of FLG and LOR expression. Knockdown of either IL-24 or STAT3 expression by small interfering RNA (siRNA) transfection augmented the upregulation of FLG and LOR expression induced by tapinarof, suggesting that inhibition of the IL-24/STAT3 axis during AHR activation supports the improvement of skin barrier dysfunction. Furthermore, tapinarof alone could restore the downregulation of FLG and LOR expression induced by IL-4, a key cytokine of AD, and its combination with JAK inhibitors enhanced this effect. These findings provide a new strategy for treating AD using AHR modulators and JAK inhibitors.

Gene regulation of filaggrin and other skin barrier proteins via aryl hydrocarbon receptor

2015 ◽  
Vol 80 (2) ◽  
pp. 83-88 ◽  
Author(s):  
Masutaka Furue ◽  
Gaku Tsuji ◽  
Chikage Mitoma ◽  
Takeshi Nakahara ◽  
Takahito Chiba ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Aryl Hydrocarbon Receptor ◽  
Skin Barrier ◽  
Aryl Hydrocarbon

scholarly journals Ochratoxin A-Induced Hepatotoxicity through Phase I and Phase II Reactions Regulated by AhR in Liver Cells

Toxins ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 377 ◽  
Author(s):  
Hye Soo Shin ◽  
Hyun Jung Lee ◽  
Min Cheol Pyo ◽  
Dojin Ryu ◽  
Kwang-Won Lee
Keyword(s):  
Oxidative Stress ◽  
Phase I ◽  
Ochratoxin A ◽  
Phase Ii ◽  
Glutathione Depletion ◽  
Related Factor ◽  
Aryl Hydrocarbon ◽  
Similar Mode ◽  
Phase I And Ii

Ochratoxin A (OTA) is a widespread mycotoxin produced by several species of the genera Aspergillus and Penicillium. OTA exists in a variety of foods, including rice, oats, and coffee and is hepatotoxic, with a similar mode of action as aflatoxin B1. The precise mechanism of cytotoxicity is not yet known, but oxidative damage is suspected to contribute to its cytotoxic effects. In this study, human hepatocyte HepG2 cells were treated with various concentrations of OTA (5–500 nM) for 48 h. OTA triggered oxidative stress as demonstrated by glutathione depletion and increased reactive oxygen species, malondialdehyde level, and nitric oxide production. Apoptosis was observed with 500 nM OTA treatment. OTA increased both the mRNA and protein expression of phase I and II enzymes. The same results were observed in an in vivo study using ICR mice. Furthermore, the relationship between phase I and II enzymes was demonstrated by the knockdown of the aryl hydrocarbon receptor (AhR) and NF-E2-related factor 2 (Nrf2) with siRNA. Taken together, our results show that OTA induces oxidative stress through the phase I reaction regulated by AhR and induces apoptosis, and that the phase II reaction is activated by Nrf2 in the presence of oxidative stress.

Exposure of human skin to benzo[a]pyrene: Role of CYP1A1 and aryl hydrocarbon receptor in oxidative stress generation

Toxicology ◽  
2010 ◽  
Vol 271 (3) ◽  
pp. 83-86 ◽  
Author(s):  
C. Costa ◽  
S. Catania ◽  
R. De Pasquale ◽  
R. Stancanelli ◽  
G.M. Scribano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aryl Hydrocarbon Receptor ◽  
Human Skin ◽  
Stress Generation ◽  
Aryl Hydrocarbon
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