Cargando…

Therapeutic Effects of Novel Sphingosine-1-Phosphate Receptor Agonist W-061 in Murine DSS Colitis

Although IL-17 is a pro-inflammatory cytokine reportedly involved in various autoimmune inflammatory disorders, its role remains unclear in murine models of colitis. Acute colitis was induced by 2.5% dextran sodium sulfate (DSS) treatment for 5 days. A novel sphingosine-1-phosphate receptor agonist...

Descripción completa

Detalles Bibliográficos
Autores principales: Sanada, Yasuaki, Mizushima, Tsunekazu, Kai, Yasuyuki, Nishimura, Junichi, Hagiya, Hiroshi, Kurata, Haruto, Mizuno, Hirotaka, Uejima, Etsuko, Ito, Toshinori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3169557/
https://www.ncbi.nlm.nih.gov/pubmed/21931623
http://dx.doi.org/10.1371/journal.pone.0023933
_version_ 1782211506312577024
author Sanada, Yasuaki
Mizushima, Tsunekazu
Kai, Yasuyuki
Nishimura, Junichi
Hagiya, Hiroshi
Kurata, Haruto
Mizuno, Hirotaka
Uejima, Etsuko
Ito, Toshinori
author_facet Sanada, Yasuaki
Mizushima, Tsunekazu
Kai, Yasuyuki
Nishimura, Junichi
Hagiya, Hiroshi
Kurata, Haruto
Mizuno, Hirotaka
Uejima, Etsuko
Ito, Toshinori
author_sort Sanada, Yasuaki
collection PubMed
description Although IL-17 is a pro-inflammatory cytokine reportedly involved in various autoimmune inflammatory disorders, its role remains unclear in murine models of colitis. Acute colitis was induced by 2.5% dextran sodium sulfate (DSS) treatment for 5 days. A novel sphingosine-1-phosphate receptor agonist W-061, a prototype of ONO-4641, was orally administered daily, and histopathological analysis was performed on the colon. The number of lymphocytes and their cytokine production were also evaluated in spleen, mesenteric lymph node, Peyer's patch and lamina propria of the colon. Daily administration of W-061 resulted in improvement of DSS-induced colitis, and significantly reduced the number of CD4+ T cells in the colonic lamina propria. Numbers of both Th17 and Th1 cells were reduced by W-061 treatment. W-061, however, had no influence on the number of Treg cells in lamina propria. Thus, Th17 and Th1 cells in lamina propria were thought to be the key subsets in the pathogenesis of DSS-induced colitis. In conclusion, W-061 may be a novel therapeutic strategy to ameliorate acute aggravation of inflammatory bowel diseases.
format Online
Article
Text
id pubmed-3169557
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-31695572011-09-19 Therapeutic Effects of Novel Sphingosine-1-Phosphate Receptor Agonist W-061 in Murine DSS Colitis Sanada, Yasuaki Mizushima, Tsunekazu Kai, Yasuyuki Nishimura, Junichi Hagiya, Hiroshi Kurata, Haruto Mizuno, Hirotaka Uejima, Etsuko Ito, Toshinori PLoS One Research Article Although IL-17 is a pro-inflammatory cytokine reportedly involved in various autoimmune inflammatory disorders, its role remains unclear in murine models of colitis. Acute colitis was induced by 2.5% dextran sodium sulfate (DSS) treatment for 5 days. A novel sphingosine-1-phosphate receptor agonist W-061, a prototype of ONO-4641, was orally administered daily, and histopathological analysis was performed on the colon. The number of lymphocytes and their cytokine production were also evaluated in spleen, mesenteric lymph node, Peyer's patch and lamina propria of the colon. Daily administration of W-061 resulted in improvement of DSS-induced colitis, and significantly reduced the number of CD4+ T cells in the colonic lamina propria. Numbers of both Th17 and Th1 cells were reduced by W-061 treatment. W-061, however, had no influence on the number of Treg cells in lamina propria. Thus, Th17 and Th1 cells in lamina propria were thought to be the key subsets in the pathogenesis of DSS-induced colitis. In conclusion, W-061 may be a novel therapeutic strategy to ameliorate acute aggravation of inflammatory bowel diseases. Public Library of Science 2011-09-08 /pmc/articles/PMC3169557/ /pubmed/21931623 http://dx.doi.org/10.1371/journal.pone.0023933 Text en Sanada et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sanada, Yasuaki
Mizushima, Tsunekazu
Kai, Yasuyuki
Nishimura, Junichi
Hagiya, Hiroshi
Kurata, Haruto
Mizuno, Hirotaka
Uejima, Etsuko
Ito, Toshinori
Therapeutic Effects of Novel Sphingosine-1-Phosphate Receptor Agonist W-061 in Murine DSS Colitis
title Therapeutic Effects of Novel Sphingosine-1-Phosphate Receptor Agonist W-061 in Murine DSS Colitis
title_full Therapeutic Effects of Novel Sphingosine-1-Phosphate Receptor Agonist W-061 in Murine DSS Colitis
title_fullStr Therapeutic Effects of Novel Sphingosine-1-Phosphate Receptor Agonist W-061 in Murine DSS Colitis
title_full_unstemmed Therapeutic Effects of Novel Sphingosine-1-Phosphate Receptor Agonist W-061 in Murine DSS Colitis
title_short Therapeutic Effects of Novel Sphingosine-1-Phosphate Receptor Agonist W-061 in Murine DSS Colitis
title_sort therapeutic effects of novel sphingosine-1-phosphate receptor agonist w-061 in murine dss colitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3169557/
https://www.ncbi.nlm.nih.gov/pubmed/21931623
http://dx.doi.org/10.1371/journal.pone.0023933
work_keys_str_mv AT sanadayasuaki therapeuticeffectsofnovelsphingosine1phosphatereceptoragonistw061inmurinedsscolitis
AT mizushimatsunekazu therapeuticeffectsofnovelsphingosine1phosphatereceptoragonistw061inmurinedsscolitis
AT kaiyasuyuki therapeuticeffectsofnovelsphingosine1phosphatereceptoragonistw061inmurinedsscolitis
AT nishimurajunichi therapeuticeffectsofnovelsphingosine1phosphatereceptoragonistw061inmurinedsscolitis
AT hagiyahiroshi therapeuticeffectsofnovelsphingosine1phosphatereceptoragonistw061inmurinedsscolitis
AT kurataharuto therapeuticeffectsofnovelsphingosine1phosphatereceptoragonistw061inmurinedsscolitis
AT mizunohirotaka therapeuticeffectsofnovelsphingosine1phosphatereceptoragonistw061inmurinedsscolitis
AT uejimaetsuko therapeuticeffectsofnovelsphingosine1phosphatereceptoragonistw061inmurinedsscolitis
AT itotoshinori therapeuticeffectsofnovelsphingosine1phosphatereceptoragonistw061inmurinedsscolitis