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IL-17A plays a central role in the expression of psoriasis signature genes through the induction of I kappa B-zeta in keratinocytes

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Title: IL-17A plays a central role in the expression of psoriasis signature genes through the induction of I kappa B-zeta in keratinocytes
Authors: Muromoto, Ryuta Browse this author →KAKEN DB
Hirao, Toru Browse this author
Tawa, Keisuke Browse this author
Hirashima, Koki Browse this author
Kon, Shigeyuki Browse this author →KAKEN DB
Kitai, Yuichi Browse this author →KAKEN DB
Matsuda, Tadashi Browse this author →KAKEN DB
Keywords: cytokine
epidermal keratinocyte
inflammation
microarray
psoriasis
Issue Date: Sep-2016
Publisher: Oxford University Press
Journal Title: International immunology
Volume: 28
Issue: 9
Start Page: 443
End Page: 452
Publisher DOI: 10.1093/intimm/dxw011
PMID: 26944069
Abstract: In psoriasis lesions, a diverse mixture of cytokines is up-regulated that influence each other generating a complex inflammatory situation. Although this is the case, the inhibition of IL-17A alone showed unprecedented clinical results in patients, indicating that IL-17A is a critical inducer of psoriasis pathogenesis. To elucidate IL-17A-driven keratinocyte-intrinsic signaling pathways, we treated monolayers of normal human epidermal keratinocytes in vitro with a mixture of six cytokines (IL-17A, TNF-alpha, IL-17C, IL-22, IL-36. and IFN-gamma) involved in psoriasis to mimic the inflammatory milieu in psoriasis lesions. Microarray and gene set enrichment analysis revealed that this cytokine mixture induced similar gene expression changes with the previous transcriptome studies using psoriasis lesions. Importantly, we identified a set of IL-17A-regulated genes in keratinocytes, which recapitulate typical psoriasis genes exemplified by DEFB4A, S100A7, IL19 and CSF3, based on the differences in the expression profiles of cells stimulated with six cytokines versus cells stimulated with only five cytokines lacking IL-17A. Furthermore, a specific IL-17A-induced gene, NFKBIZ, which encodes I kappa B-zeta, a transcriptional regulator for NF-kappa B, was demonstrated to have a significant role for IL-17A-induced gene expression. Thus, we present novel in vitro data from normal human keratinocytes that would help elucidating the IL-17A-driven keratinocyte activation in psoriasis.
Rights: This is a pre-copyedited, author-produced PDF of an article accepted for publication in International immunology following peer review. The version of record Int. Immunol. (2016) 28(9):443-452, is available online at: http://dx.doi.org/10.1093/intimm/dxw011
Type: article (author version)
URI: http://hdl.handle.net/2115/67074
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 室本 竜太

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