title: IL-17A upregulates keratin 17 expression in keratinocytes through STAT1- and STAT3-dependent mechanisms.
abstract: Psoriasis, an immunological skin disease, is characterized by epidermal hyperproliferation, chronic inflammation, and an accumulation of infiltrating T cells. IL-17A is a key cytokine that has a critical role in the pathogenesis of psoriasis. Keratin 17 (K17) is strongly expressed in psoriatic lesions but not in normal skin. Thus, K17 expression is regarded as a hallmark of psoriasis. We previously reported that the K17/T cells/cytokine autoimmune loop was involved in psoriasis. However, the relationship between IL-17A and K17 has yet to be determined. In the present study, IL-17A-induced K17 expression was confirmed in cultured keratinocytes in both mRNA and protein levels. In addition, increased K17 expression was found in the epidermis of IL-17A-injected mouse skin. The regulatory mechanism of K17 expression was further investigated. We found that both the signal transducer and activator of transcription (STAT) 1 and STAT3 pathways were involved in the upregulation of K17 expression induced by IL-17A, and that such regulation could be partially suppressed by STAT1 or STAT3 small interfering RNA and inhibitor. Our data suggest that IL-17A can upregulate K17 expression in keratinocytes in a dose-dependent manner through STAT1- and STAT3-dependent mechanisms. The results indicate that IL-17A might be an important cytokine in the K17/T cells/cytokine autoimmune loop associated with psoriasis.
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Shi
authors.forename: Liang
authors.initials: L
authors.lastname: Jin
authors.forename: Erle
authors.initials: E
authors.lastname: Dang
authors.forename: Ting
authors.initials: T
authors.lastname: Chang
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Feng
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053537:Keratin-17 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D034741:RNA, Small Interfering / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; C508717:IL17A protein, human; D020381:Interleukin-17; D053537:Keratin-17; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D014740:Vidarabine; C024352:fludarabine