IL-10 Inhibits Transforming Growth Factor-ß-Induction of Type I Collagen mRNA Expression via Both JNK and p38 Pathways in Human Lung Fibroblasts

Arai, Toru; Hirata, Haruhiko; Hoshino, Shigenori; Inoue, Koji; Kawase, Ichiro; Kida, Hiroshi; Kijima, Takashi; Kumagai, Toru; Osaki, Tadashi; Tachibana, Isao; Takimoto, Takayuki; Yanagita, Masahiko; Yano, Yukihiro; Yoshida, Mitsuhiro

IL-10 Inhibits Transforming Growth Factor-ß-Induction of Type I Collagen mRNA Expression via Both JNK and p38 Pathways in Human Lung Fibroblasts

dc.contributor.author	Arai, Toru	de
dc.contributor.author	Hirata, Haruhiko	de
dc.contributor.author	Hoshino, Shigenori	de
dc.contributor.author	Inoue, Koji	de
dc.contributor.author	Kawase, Ichiro	de
dc.contributor.author	Kida, Hiroshi	de
dc.contributor.author	Kijima, Takashi	de
dc.contributor.author	Kumagai, Toru	de
dc.contributor.author	Osaki, Tadashi	de
dc.contributor.author	Tachibana, Isao	de
dc.contributor.author	Takimoto, Takayuki	de
dc.contributor.author	Yanagita, Masahiko	de
dc.contributor.author	Yano, Yukihiro	de
dc.contributor.author	Yoshida, Mitsuhiro	de
dc.date.accessioned	2008-06-17T13:57:51Z
dc.date.available	2008-06-17T13:57:51Z
dc.date.issued	2005-08-11	de
dc.description.abstract	Transforming growth factor-ß (TGF-ß) is a key factor for understanding the pathogenesis of fibrotic disorders such as idiopathic pulmonary fibrosis (IPF). We have demonstrated that interleukin-10 (IL-10) suppresses TGF-ß-induced expression of type I collagen (COL1) mRNA in a human lung fibroblast cell line (WI-38). However, the inhibitory mechanism has not yet been clearly elucidated. Thus, in the current study, we investigate the effects of IL-10 blockade of TGF-ß signaling which regulates COL1 mRNA expression. In WI-38 cells, IL-10 inhibits TGF-ß-mediated phosphorylation of both, c-Jun HN2-terminal kinase (JNK) and p38, but does not suppress TGF-ß- mediated phosphorylation of Smad2 or affect TGF-ß-upregulation of Smad7 mRNA expression. In addition, SP600125 and SB203580, specific inhibitors of JNK and p38, respectively, attenuate TGF-ß-induced COL1 mRNA expression in WI-38 cells. These results suggest that IL-10 inhibits TGF-ß-induced COL1 mRNA expression via both JNK and p38 pathways but not Smad pathways in WI-38 cells. This inhibitory mechanism may provide a novel insight into therapeutic strategies for fibrotic disorders such as IPF.	en
dc.identifier.issn	1611-2156	de
dc.identifier.uri	http://hdl.handle.net/2003/25650
dc.identifier.uri	http://dx.doi.org/10.17877/DE290R-8281
dc.language.iso	en	de
dc.relation.ispartofseries	EXCLI Journal ; Vol. 4, 2005	en
dc.subject	collagen	en
dc.subject	IL-10	en
dc.subject	JNK	en
dc.subject	Smad	en
dc.subject	TGF-ß	en
dc.subject.ddc	610
dc.title	IL-10 Inhibits Transforming Growth Factor-ß-Induction of Type I Collagen mRNA Expression via Both JNK and p38 Pathways in Human Lung Fibroblasts	en
dc.type	Text	de
dc.type.publicationtype	article	de
dcterms.accessRights	open access
eldorado.dnb.zdberstkatid	2132560-1

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