1. 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Regulates the Expression of Aryl Hydrocarbon Receptor-Related Factors and Cytokines in Peripheral Blood Mononuclear Cells and CD4+ T cells from Patients with Atopic Dermatitis and Psoriasis
- Author
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Hye One Kim, Han Bi Kim, Jee Hee Son, Bo Young Chung, Ji-Young Um, Chun Wook Park, and Seok Young Kang
- Subjects
atopic ,medicine.medical_treatment ,Dermatitis ,Dermatology ,6-formyl indolo [3,2-b] carbazole (FICZ) psoriasis ,Peripheral blood mononuclear cell ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Psoriasis ,Gene expression ,medicine ,aryl hydrocarbon ,Receptor ,biology ,business.industry ,Interleukin ,respiratory system ,medicine.disease ,Aryl hydrocarbon receptor ,Polychlorinated dibenzodioxins ,Molecular biology ,respiratory tract diseases ,Cytokine ,030220 oncology & carcinogenesis ,biology.protein ,Original Article ,business - Abstract
Background Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is important for xenobiotic metabolism and binds to various endogenous and exogenous ligands in the skin. However, the functional role of AhR in patients with psoriasis (PS) and atopic dermatitis (AD) remains unclear. Objective We aimed to determine whether AhR-regulated factors (AhR, CYP1A1, interleukin [IL]-17, IL-22) were affected by AhR ligands (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) in chronic inflammatory skin diseases such as PS and AD. Methods The expression levels of AhR-related factors were determined by quantitative PCR, western blotting, and immunocytochemistry. Specific siRNA targeting AhR was used to inhibit gene expression in human peripheral blood mononuclear cells (PBMC). Cytokine assays were performed to determine the protein production of CD4+ T cells. Results In comparison with healthy controls, TCDD-treated PBMCs and CD4+ T cells from patients with PS and AD showed an increase in AhR gene levels as well as significantly increased expression of AhR-related factors (such as AhR, CYP1A1, IL-17, and IL-22). In contrast, 6-formyl indolo [3,2-b] carbazole (FICZ) inversely affected the differentiation of CD4+ T cells and their cytokine expression levels as compared with TCDD. CD4+ T cells from patients with AD and PS showed higher expression levels of AhR, CYP1A1, IL-17, and IL-22. Conclusion Our results suggest that TCDD-induced AhR-related factor upregulation in AD and PS patients may increase the expression of AhR-regulatory genes, thereby contributing to the development of AD and PS.
- Published
- 2020