Decreases in 15-lipoxygenase metabolites in Olmsted syndrome model rats

Wakabayashi, Masato; Yoshioka, Takeshi; Higashino, Kenichi; Numata, Yoshito; Igarashi, Yasuyuki; Kihara, Akio

Decreases in 15-lipoxygenase metabolites in Olmsted syndrome model rats

Wakabayashi, Masato; Yoshioka, Takeshi; Higashino, Kenichi et al.

Journal of dermatological science, 2017, 85(3), 186-196

Permalink : https://hdl.handle.net/2115/68655

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アクセス権	open access
URI	https://hdl.handle.net/2115/68655
タイトル	Decreases in 15-lipoxygenase metabolites in Olmsted syndrome model rats
著者	Wakabayashi, Masato ; Yoshioka, Takeshi ; Higashino, Kenichi ; Numata, Yoshito ; Igarashi, Yasuyuki ; Kihara, Akio
著者名 Wakabayashi, Masato
著者名 Yoshioka, Takeshi
著者名 Higashino, Kenichi
著者名 Numata, Yoshito
著者名 Igarashi, Yasuyuki
e-Rad_Researcher 50333620 著者名 Kihara, Akio
言語	英語
キーワード	Lipid
	Lipidomics
	15-Lipoxygenase
	Olmsted syndrome
	TRPV3
発行日	2017-03
出版者	Elsevier
収録物名	Journal of dermatological science
巻(号)	85(3)
ページ	186-196
抄録	Background: Olmsted syndrome (OS) is a congenital dermatosis characterized by palmoplantar keratoderma and periorificial keratotic plaque. TRPV3 (transient receptor potential vanilloid subtype 3) encodes a thermosensitive Ca2+ channel and is the causative gene of OS. However, the molecular mechanism that causes the pathological development of OS is unclear. Objective: We aimed to investigate the molecular mechanisms underlying OS pathology from the perspective of lipid metabolism. Methods: Comprehensive lipidomics and microarray analyses were conducted on tissue samples from a non-lesional skin area of OS model rats (Ht rats) and from wild type (WT) rats as the control. Results: Infiltration of leukocytes such as eosinophils and neutrophils and an increase in the fibrotic region were detected in the unaffected skin area of Ht rats compared with the WT rats. Among about 600 lipid species examined, the levels of 15-lipoxygenase (LOX) metabolites, the precursors of anti-inflammatory and pro-resolving lipid mediators, and dihydroceramides decreased by >= 16-fold in Ht rats compared with WT rats: Consistent with the decreases in the 15-LOX metabolites, expression levels of the genes that encode the 15-LOXs, Alox15 and Alox15b, were largely reduced. Conversely, increased expression levels were detected of 1136b, Cc120, Cxcl1, and Cxcl2, which encode cytokines/chemokines, and S100a8 and S100a9, which encode the Ca2+ binding proteins that are implicated in epidermal proliferation. Conclusion: The pro-inflammatory state in the unaffected skin of Ht rats caused by decreases in 15-LOX metabolites and increases in cytokines/chemokines may contribute to the pathogenesis of OS. (C) 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	©2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0923-1811
関連情報	PMID 28024685
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.jdermsci.2016.12.013