title: The inhibitory effect of A20 on the inflammatory reaction of epidermal keratinocytes.
abstract: A20 is a negative regulator of nuclear factor κ-light‑chain-enhancer of activated B cells (NF-κB) signaling, and has been implicated in the pathogenesis of psoriasis through genome-wide association study (GWAS). In the present study, we investigated the putative role of A20 in epidermal keratinocytes. Immunohistochemical analysis showed that A20 was expressed in all layers of the epidermis, with an increasing pattern in the upper layers. In our model of calcium-induced keratinocyte differentiation, A20 expression was increased in a time-dependent manner. To investigate whether A20 affected keratinocyte differentiation, we overexpressed A20 in cultured keratinocytes. As a result, we noted that A20 overexpression did not affect keratinocyte differentiation, suggesting that A20 is not a direct modulator of keratinocyte differentiation. Interestingly, we found that A20 levels were decreased in psoriatic lesional skin compared to non-lesional areas. To investigate whether A20 played a role in the innate immune response of keratinocytes, we overexpressed A20 and then examined poly(I:C)-induced cytokine expression. We noted that A20 significantly inhibited poly(I:C)-induced cytokine production, and this effect was related to the inhibition of NF-κB signaling. These results suggest that the downregulation of A20 increased the susceptibility of keratinocytes to external stimuli, thus contributing to the development of psoriasis.
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Kyung-Cheol
authors.initials: KC
authors.lastname: Sohn
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Seung Ju
authors.initials: SJ
authors.lastname: Back
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Dae-Kyoung
authors.initials: DK
authors.lastname: Choi
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Shin
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Sue Jeong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Myung
authors.initials: M
authors.lastname: Im
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Seo
authors.affiliation: Department of Dermatology, School of Medicine, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Yoon
authors.affiliation: Department of Anatomy, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Jeung-Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Chang Deok
authors.initials: CD
authors.lastname: Kim
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D015603:Keratinocytes / Q000166:cytology* / Q000276:immunology; D016328:NF-kappa B / Q000032:analysis / Q000276:immunology; D011565:Psoriasis / Q000276:immunology; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000032:analysis / Q000276:immunology*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3