Protective role of resolvin D1, a pro-resolving lipid mediator, in nonsteroidal anti-inflammatory drug-induced small intestinal damage.

Resolvin D1, a specialized pro-resolving lipid mediator produced from docosahexaenoic acid by 15- and 5-lipoxygenase, exerts anti-inflammatory effects driving to the resolution of inflammation. The present study aimed to elucidate its role in small intestinal damage induced by nonsteroidal anti-infl...

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Autores principales:	Takuya Kuzumoto, Tetsuya Tanigawa, Akira Higashimori, Hiroyuki Kitamura, Yuji Nadatani, Koji Otani, Shusei Fukunaga, Shuhei Hosomi, Fumio Tanaka, Noriko Kamata, Yasuaki Nagami, Koichi Taira, Toshio Watanabe, Yasuhiro Fujiwara
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6bb02232e6194015b5f31de0a4759d2d
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spelling	oai:doaj.org-article:6bb02232e6194015b5f31de0a4759d2d2021-11-25T06:19:23ZProtective role of resolvin D1, a pro-resolving lipid mediator, in nonsteroidal anti-inflammatory drug-induced small intestinal damage.1932-620310.1371/journal.pone.0250862https://doaj.org/article/6bb02232e6194015b5f31de0a4759d2d2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0250862https://doaj.org/toc/1932-6203Resolvin D1, a specialized pro-resolving lipid mediator produced from docosahexaenoic acid by 15- and 5-lipoxygenase, exerts anti-inflammatory effects driving to the resolution of inflammation. The present study aimed to elucidate its role in small intestinal damage induced by nonsteroidal anti-inflammatory drug (NSAID). Indomethacin was administered orally to C57BL/6J male mice, which were sacrificed 24 h later to collect small intestine specimens. Before administration of indomethacin, mice were subjected to intraperitoneal treatment with resolvin D1 or oral administration of baicalein, a 15-lipoxygenase inhibitor. Small intestinal damage induced by indomethacin was attenuated by pretreatment with resolvin D1. Furthermore, resolvin D1 reduced the gene expression levels of interleukin-1β, tumor necrosis factor-α, and CXCL1/keratinocyte chemoattractant. Conversely, the inhibition of 15-lipoxygenase activity by baicalein increased the expression of genes coding for these inflammatory cytokines and chemokine, leading to exacerbated small intestinal damage, and reduced the concentration of resolvin D1 in the small intestinal tissue. Exogenous treatment with resolvin D1 negated the deleterious effect of baicalein. 15-lipoxygenase was mainly expressed in the epithelium and inflammatory cells of the small intestine, and its gene and protein expression was not affected by the administration of indomethacin. Inhibition of the resolvin D1 receptor, lipoxin A4 receptor /formyl peptide receptor 2, by its specific inhibitors Boc-1 and WRW4 aggravated indomethacin-induced small intestinal damage. Collectively, these results indicate that resolvin D1 produced by 15-lipoxygenase contributes to mucoprotection against NSAID-induced small intestinal damage through its anti-inflammatory effect.Takuya KuzumotoTetsuya TanigawaAkira HigashimoriHiroyuki KitamuraYuji NadataniKoji OtaniShusei FukunagaShuhei HosomiFumio TanakaNoriko KamataYasuaki NagamiKoichi TairaToshio WatanabeYasuhiro FujiwaraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0250862 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takuya Kuzumoto Tetsuya Tanigawa Akira Higashimori Hiroyuki Kitamura Yuji Nadatani Koji Otani Shusei Fukunaga Shuhei Hosomi Fumio Tanaka Noriko Kamata Yasuaki Nagami Koichi Taira Toshio Watanabe Yasuhiro Fujiwara Protective role of resolvin D1, a pro-resolving lipid mediator, in nonsteroidal anti-inflammatory drug-induced small intestinal damage.
description	Resolvin D1, a specialized pro-resolving lipid mediator produced from docosahexaenoic acid by 15- and 5-lipoxygenase, exerts anti-inflammatory effects driving to the resolution of inflammation. The present study aimed to elucidate its role in small intestinal damage induced by nonsteroidal anti-inflammatory drug (NSAID). Indomethacin was administered orally to C57BL/6J male mice, which were sacrificed 24 h later to collect small intestine specimens. Before administration of indomethacin, mice were subjected to intraperitoneal treatment with resolvin D1 or oral administration of baicalein, a 15-lipoxygenase inhibitor. Small intestinal damage induced by indomethacin was attenuated by pretreatment with resolvin D1. Furthermore, resolvin D1 reduced the gene expression levels of interleukin-1β, tumor necrosis factor-α, and CXCL1/keratinocyte chemoattractant. Conversely, the inhibition of 15-lipoxygenase activity by baicalein increased the expression of genes coding for these inflammatory cytokines and chemokine, leading to exacerbated small intestinal damage, and reduced the concentration of resolvin D1 in the small intestinal tissue. Exogenous treatment with resolvin D1 negated the deleterious effect of baicalein. 15-lipoxygenase was mainly expressed in the epithelium and inflammatory cells of the small intestine, and its gene and protein expression was not affected by the administration of indomethacin. Inhibition of the resolvin D1 receptor, lipoxin A4 receptor /formyl peptide receptor 2, by its specific inhibitors Boc-1 and WRW4 aggravated indomethacin-induced small intestinal damage. Collectively, these results indicate that resolvin D1 produced by 15-lipoxygenase contributes to mucoprotection against NSAID-induced small intestinal damage through its anti-inflammatory effect.
format	article
author	Takuya Kuzumoto Tetsuya Tanigawa Akira Higashimori Hiroyuki Kitamura Yuji Nadatani Koji Otani Shusei Fukunaga Shuhei Hosomi Fumio Tanaka Noriko Kamata Yasuaki Nagami Koichi Taira Toshio Watanabe Yasuhiro Fujiwara
author_facet	Takuya Kuzumoto Tetsuya Tanigawa Akira Higashimori Hiroyuki Kitamura Yuji Nadatani Koji Otani Shusei Fukunaga Shuhei Hosomi Fumio Tanaka Noriko Kamata Yasuaki Nagami Koichi Taira Toshio Watanabe Yasuhiro Fujiwara
author_sort	Takuya Kuzumoto
title	Protective role of resolvin D1, a pro-resolving lipid mediator, in nonsteroidal anti-inflammatory drug-induced small intestinal damage.
title_short	Protective role of resolvin D1, a pro-resolving lipid mediator, in nonsteroidal anti-inflammatory drug-induced small intestinal damage.
title_full	Protective role of resolvin D1, a pro-resolving lipid mediator, in nonsteroidal anti-inflammatory drug-induced small intestinal damage.
title_fullStr	Protective role of resolvin D1, a pro-resolving lipid mediator, in nonsteroidal anti-inflammatory drug-induced small intestinal damage.
title_full_unstemmed	Protective role of resolvin D1, a pro-resolving lipid mediator, in nonsteroidal anti-inflammatory drug-induced small intestinal damage.
title_sort	protective role of resolvin d1, a pro-resolving lipid mediator, in nonsteroidal anti-inflammatory drug-induced small intestinal damage.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/6bb02232e6194015b5f31de0a4759d2d
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Protective role of resolvin D1, a pro-resolving lipid mediator, in nonsteroidal anti-inflammatory drug-induced small intestinal damage.

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