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Aryl hydrocarbon receptor skin

Martina Stepankova, Barbora Pastorkova, Petr Bachleda, Zdenek Dvorak
Triazole antimycotic itraconazole contains in its structure three chiral centres; therefore, it forms eight stereoisomers. Commercial preparations of itraconazole are a mixture of four cis-diastereoisomers. There is much evidence that efficacy, adverse effects, and toxicity of chiral drugs may be stereospecific. Therefore, we have prepared 4 pure cis-diastereoisomers of itraconazole and investigated their effects on transcriptional activities of xenoreceptors aryl hydrocarbon receptor AhR and pregnane X receptor PXR...
April 5, 2017: Toxicology
Susanne Koch, Tim J Stroisch, Julia Vorac, Nadine Herrmann, Nicole Leib, Sylvia Schnautz, Helene Kirins, Irmgard Förster, Heike Weighardt, Thomas Bieber
BACKGROUND: Aryl hydrocarbon receptor (AhR), an important regulator of immune responses, is activated by UVB irradiation in the skin. Langerhans cells (LC) in the epidermis of atopic dermatitis (AD) patients carry the high affinity receptor for IgE, FcεRI, and are crucially involved in the pathogenesis of AD by inducing inflammatory responses and regulating tolerogenic processes. OBJECTIVES: We investigated AhR and AhR repressor (AhRR) expression and functional consequences of AhR activation in human ex vivo skin cells and in in vitro generated LC...
April 4, 2017: Allergy
Masutaka Furue, Hiroshi Uchi, Chikage Mitoma, Akiko Hashimoto-Hachiya, Takahito Chiba, Takamichi Ito, Takeshi Nakahara, Gaku Tsuji
Skin is the outermost part of the body and is, thus, inevitably exposed to UV rays and environmental pollutants. Oxidative stress by these hazardous factors accelerates skin aging and induces skin inflammation and carcinogenesis. Aryl hydrocarbon receptors (AHRs) are chemical sensors that are abundantly expressed in epidermal keratinocytes and mediate the production of reactive oxygen species. To neutralize or minimize oxidative stress, the keratinocytes also express nuclear factor-erythroid 2-related factor-2 (NRF2), which is a master switch for antioxidant signaling...
March 3, 2017: Nutrients
Andrew Sullivan, Eryi Wang, John Farrell, Paul Whitaker, Lee Faulkner, Daniel Peckham, B Kevin Park, Dean J Naisbitt
BACKGROUND: β-Lactam hypersensitivity has been classified according to the phenotype and function of drug-specific T cells. However, new T-cell subsets have not been considered. OBJECTIVE: The objective of this study was to use piperacillin as a model of β-lactam hypersensitivity to study the nature of the drug-specific T-cell response induced in the blood and skin of hypersensitive patients and healthy volunteers. METHODS: Drug-specific T cells were cloned from blood and inflamed skin, and cellular phenotype and function were explored...
February 20, 2017: Journal of Allergy and Clinical Immunology
Kazuhiko Yamamura, Takehito Uruno, Akira Shiraishi, Yoshihiko Tanaka, Miho Ushijima, Takeshi Nakahara, Mayuki Watanabe, Makiko Kido-Nakahara, Ikuya Tsuge, Masutaka Furue, Yoshinori Fukui
Mutations of DOCK8 in humans cause a combined immunodeficiency characterized by atopic dermatitis with high serum IgE levels. However, the molecular link between DOCK8 deficiency and atopic skin inflammation is unknown. Here we show that CD4(+) T cells from DOCK8-deficient mice produce large amounts of IL-31, a major pruritogen associated with atopic dermatitis. IL-31 induction critically depends on the transcription factor EPAS1, and its conditional deletion in CD4(+) T cells abrogates skin disease development in DOCK8-deficient mice...
January 9, 2017: Nature Communications
Masutaka Furue, Takahito Chiba, Gaku Tsuji, Dugarmaa Ulzii, Makiko Kido-Nakahara, Takeshi Nakahara, Takafumi Kadono
Atopic dermatitis (AD) is a chronic or chronically relapsing, eczematous, severely pruritic skin disorder mostly associated with IgE elevation and skin barrier dysfunction due to decreased filaggrin expression. The lesional skin of AD exhibits Th2- and Th22-deviated immune reactions that are progressive during disease chronicity. Th2 and Th22 cytokines further deteriorate the skin barrier by inhibiting filaggrin expression. Some IgEs are reactive to self-antigens. The IgE autoreactivity may precipitate the chronicity of AD...
January 2, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
Wenshan Gao, Jingze Tan, Anke Hüls, Anan Ding, Yu Liu, Mary S Matsui, Andrea Vierkötter, Jean Krutmann, Tamara Schikowski, Li Jin, Sijia Wang
BACKGROUND: The progression and manifestation of human skin aging has a strong genetic basis; however, most of the supporting evidence has been gathered in Caucasian populations. The genetic contribution to the variation in skin aging in non-Caucasian populations is poorly understood. OBJECTIVE: To investigate the genetic risk factors of relevance for skin aging in East Asians, we conducted the first candidate gene study for signs of skin aging in Han Chinese. METHODS: We collected skin aging and genotype data in 502 female Han Chinese from the Taizhou cohort...
April 2017: Journal of Dermatological Science
Sabiya Abbas, Shamshad Alam, Krishna P Singh, Mahadeo Kumar, Shailendra K Gupta, Kausar M Ansari
Benzanthrone (BA), an oxidized polycyclic aromatic hydrocarbon (PAH), has been found to be a potential health threat to occupational workers involved in dye manufacturing factories. It has been observed that occupational workers become exposed to BA either during manufacturing, pulverization, or storage and developed various kinds of skin diseases like contact dermatitis, itching, erythema, roughness, and foremost, hyperpigmentation. It has been shown that some environmental organic pollutants (POPs) like dioxins, furans, and polychlorinated biphenyls (PCBs) may act as ligands for the aryl hydrocarbon receptor (AhR) and regulate hyperpigmentation...
February 20, 2017: Chemical Research in Toxicology
Hiroshi Uchi, Mao Yasumatsu, Saori Morino-Koga, Chikage Mitoma, Masutaka Furue
BACKGROUND: Dioxins and other environmental pollutants are toxic and remain in biological tissues for a long time leading to various levels of oxidative stress. Although the toxicity of these agents has been linked to activation of the aryl hydrocarbon receptor (AHR), no effective treatment has been developed. OBJECTIVE: To explore novel phytochemicals that inhibit AHR activation in keratinocytes. METHODS: Keratinocytes were used in this study because the skin is one of the organs most affected by dioxin and other environmental pollutants...
January 2017: Journal of Dermatological Science
Luhua H Zhang, June Ho Shin, Mikel D Haggadone, John B Sunwoo
A tissue-resident population of natural killer cells (NK cells) in the liver has recently been described to have the unique capacity to confer immunological memory in the form of hapten-specific contact hypersensitivity independent of T and B cells. Factors regulating the development and maintenance of these liver-resident NK cells are poorly understood. The aryl hydrocarbon receptor (AhR) is a transcription factor modulated by exogenous and endogenous ligands that is important in the homeostasis of immune cells at barrier sites, such as the skin and gut...
October 17, 2016: Journal of Experimental Medicine
Motoki Nakamura, Emi Nishida, Akimichi Morita
The aryl hydrocarbon receptor (AHR) mediates melanocyte activation and skin tanning. We hypothesized that the AHR also mediates melanoblast-to-melanocyte maturation. In a cloned cell line, NCCmelb4, derived from mouse neural crest cells, we investigated AHR expression in melanoblasts stimulated by UV irradiation and AHR agonists. We irradiated the cells with UV, ranging from 280 to 380 nm in 10-nm increments, using a multiwavelength irradiation spectral apparatus. Tyrosinase expression significantly increased with bimodal peaks at 310 and 360 nm...
August 2016: Experimental Dermatology
Katharina Haas, Heike Weighardt, René Deenen, Karl Köhrer, Björn Clausen, Sonja Zahner, Petra Boukamp, Wilhelm Bloch, Jean Krutmann, Charlotte Esser
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in adaptive cell functions, and is highly active in the epidermis. AhR ligands can accelerate keratinocyte differentiation, but the precise role of AhR in the skin barrier is unknown. Our study showed that transepidermal water loss (TEWL), a parameter of skin barrier integrity, is high in AhR-deficient (AhR-KO) mice. Experiments with conditionally AhR-deficient mouse lines identified keratinocytes as the primary cell population responsible for high TEWL...
July 15, 2016: Journal of Investigative Dermatology
Danay Cibrian, María Laura Saiz, Hortensia de la Fuente, Raquel Sánchez-Díaz, Olga Moreno-Gonzalo, Inmaculada Jorge, Alessia Ferrarini, Jesús Vázquez, Carmen Punzón, Manuel Fresno, Miguel Vicente-Manzanares, Esteban Daudén, Pedro M Fernández-Salguero, Pilar Martín, Francisco Sánchez-Madrid
The activation marker CD69 is expressed by skin γδ T cells. Here we found that CD69 controlled the aryl hydrocarbon receptor (AhR)-dependent secretion of interleukin 22 (IL-22) by γδ T cells, which contributed to the development of psoriasis induced by IL-23. CD69 associated with the aromatic-amino-acid-transporter complex LAT1-CD98 and regulated its surface expression and uptake of L-tryptophan (L-Trp) and the intracellular quantity of L-Trp-derived activators of AhR. In vivo administration of L-Trp, an inhibitor of AhR or IL-22 abrogated the differences between CD69-deficient mice and wild-type mice in skin inflammation...
August 2016: Nature Immunology
Qiang Ju, Christos C Zouboulis
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...
September 2016: Reviews in Endocrine & Metabolic Disorders
Chiang-Wen Lee, Zih-Chan Lin, Stephen Chu-Sung Hu, Yao-Chang Chiang, Lee-Fen Hsu, Yu-Ching Lin, I-Ta Lee, Ming-Horng Tsai, Jia-You Fang
We explored the regulation of filaggrin, cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) expression induced by urban particulate matter (PM) in human keratinocytes. In addition, we investigated the signaling pathways involved in PM-induced effects on COX2/PGE2 and filaggrin. PMs induced increases in COX2 expression and PGE2 production, and decreased filaggrin expression. These effects were attenuated by pretreatment with COX2 inhibitor and PGE2 receptor antagonist, or after transfection with siRNAs of the aryl hydrocarbon receptor (AhR), gp91phox and p47phox...
2016: Scientific Reports
Olga Brandstätter, Oliver Schanz, Julia Vorac, Jessica König, Tetsushi Mori, Toru Maruyama, Markus Korkowski, Thomas Haarmann-Stemmann, Dorthe von Smolinski, Joachim L Schultze, Josef Abel, Charlotte Esser, Haruko Takeyama, Heike Weighardt, Irmgard Förster
As a sensor of polyaromatic chemicals the aryl hydrocarbon receptor (AhR) exerts an important role in immune regulation besides its requirement for xenobiotic metabolism. Transcriptional activation of AhR target genes is counterregulated by the AhR repressor (AhRR) but the exact function of the AhRR in vivo is currently unknown. We here show that the AhRR is predominantly expressed in immune cells of the skin and intestine, different from other AhR target genes. Whereas AhRR antagonizes the anti-inflammatory function of the AhR in the context of systemic endotoxin shock, AhR and AhRR act in concert to dampen intestinal inflammation...
2016: Scientific Reports
Chien-Hui Hong, Chih-Hung Lee, Hsin-Su Yu, Shau-Ku Huang
BACKGROUND: Atopic dermatitis (AD) is a common disease with genetic and environmental interactions. We previously reported lifetime exposure to cigarette smoke is associated with adult-onset AD. Aryl hydrocarbon receptor (AhR) is important in regulating environmental exposure to xenobiotics, including benzopyrenes (BP), a major polycyclic aromatic hydrocarbon (PAH) present in cigarette smoke. However, how AhR regulates immune responses in sensitization phase of AD remained elusive. METHODS: We investigated how BP affects epicutaneous sensitization response through AhR axis...
July 2016: International Immunopharmacology
Anna Smirnova, Emma Wincent, Linda Vikström Bergander, Tomas Alsberg, Jan Bergman, Agneta Rannug, Ulf Rannug
Activation of the aryl hydrocarbon receptor (AhR), a conserved transcription factor best known as a target for highly toxic halogenated substances such as dioxin, under normal xenobiotic-free conditions is of considerable scientific interest. We have demonstrated previously that a photoproduct of tryptophan, 6-formylindolo[3,2-b]carbazole (FICZ), fulfills the criteria for an endogenous ligand for this receptor and proposed that this compound is the enigmatic mediator of the physiological functions of AhR. Here, we describe novel light-independent pathways by which FICZ can be formed...
January 19, 2016: Chemical Research in Toxicology
Claudia Skazik-Voogt, Katrin Kühler, Hagen Ott, Katharina Czaja, Gabriele Zwadlo-Klarwasser, Hans F Merk, Philipp M Amann, Jens M Baron
Primary dendritic cells and myeloid cell lines are used to assess the skin sensitization hazard in in vitro approaches. The aryl hydrocarbon receptor (AhR) modulates expression of CYP enzymes which play a significant role in the bioactivation of various xenobiotics. These studies revealed a strong constitutive expression of the AhR in primary human monocytes, monocyte-derived immature dendritic cells (iDC) and cord blood-derived Langerhans cells (LC). In contrast, mRNA and protein expression of AhR was hardly detectable in the cell lines THP-1 and MUTZ-3...
2016: ALTEX
Gabriella Fabbrocini, Gürkan Kaya, Patricia Caseiro Silverio, Valerio De Vita, Aysin Kaya, Fabienne Fontao, Olivier Sorg, Jean-Hilaire Saurat
BACKGROUND: Dioxins are persistent organic pollutants present in the environment. They exert their biological effects by binding to an intracellular receptor, the aryl hydrocarbon receptor (AhR). Activation of AhR leads to the induction of cytochrome p450 1A1 (CYP1A1). Expression of CYP1A1 in human skin is a key marker for AhR activation, and it may induce comedogenesis resulting in acne-like lesions known as chloracne/metabolising acquired dioxin-induced skin hamartomas (MADISH). The contribution of this pathway in patients seen in a busy acne clinic is unknown...
2015: Dermatology: International Journal for Clinical and Investigative Dermatology
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