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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

Annals of Dermatology 2020년 32권 5호 p.360 ~ 369
Um Ji-Young, 김한비, 강석영, 손지희, 정보영, 박천욱, 김혜원,
소속 상세정보
 ( Um Ji-Young ) - Hallym University College of Medicine Kangnam Sacred Heart Hospital Department of Dermatology
김한비 ( Kim Han-Bi ) - Hallym University College of Medicine Kangnam Sacred Heart Hospital Department of Dermatology
강석영 ( Kang Seok-Young ) - Hallym University College of Medicine Kangnam Sacred Heart Hospital Department of Dermatology
손지희 ( Son Jee-Hee ) - Hallym University College of Medicine Kangnam Sacred Heart Hospital Department of Dermatology
정보영 ( Chung Bo-Young ) - Hallym University College of Medicine Kangnam Sacred Heart Hospital Department of Dermatology
박천욱 ( Park Chun-Wook ) - Hallym University College of Medicine Kangnam Sacred Heart Hospital Department of Dermatology
김혜원 ( Kim Hye-One ) - Hallym University College of Medicine Kangnam Sacred Heart Hospital Department of Dermatology

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.

키워드

6-formyl indolo [3,2-b] carbazole (FICZ) psoriasis; Dermatitis; atopic; Polychlorinated dibenzodioxins; Psoriasis; Receptor; aryl hydrocarbon

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