Anti-fibrotic Effects of ONO-EF-345, a Specific Phosphodiesterase IV inhibitor, on Lung Fibroblasts

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

Anti-fibrotic Effects of ONO-EF-345, a Specific Phosphodiesterase IV inhibitor, on Lung Fibroblasts

dc.contributor.author	Hirata, Haruhiko	de
dc.contributor.author	Hoshino, Shigenori	de
dc.contributor.author	Inoue, Koji	de
dc.contributor.author	Kashiwa, Yozo	de
dc.contributor.author	Kawase, Ichiro	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	2008-06-17T14:13:47Z
dc.date.available	2008-06-17T14:13:47Z
dc.date.issued	2007-02-24	de
dc.description.abstract	Phosphodiesterase (PDE) IV inhibitors have been shown to inhibit various inflammatory reactions in pulmonary diseases such as bronchial asthma and chronic obstructive lung diseases (COPD). However, there have been no studies evaluating the effect of PDE IV inhibitors on airway fibrosis, which is a critical feature of airway remodeling in asthma and COPD. We therefore examined whether ONO-EF-345 (ONO), a PDE IV inhibitor, affected the function of lung fibroblasts. ONO suppressed TGF-ß-induced type I collagen (COL1) mRNA expression in lung fibroblasts and also inhibited TGF-ß-induced a- smooth muscle actin (SMA) protein expression. ONO did not affect Smad2 phosphorylation or Smad7 expression. However, ONO reduced JNK and p38 activation, which regulates TGF-ß-induced COL1 expression. These results indicate that PDE IV inhibitors exert anti-fibrotic effects through the JNK and/or p38 pathways.	en
dc.identifier.issn	1611-2156	de
dc.identifier.uri	http://hdl.handle.net/2003/25680
dc.identifier.uri	http://dx.doi.org/10.17877/DE290R-8186
dc.language.iso	en	de
dc.relation.ispartofseries	EXCLI Journal ; Vol. 6, 2007	en
dc.subject	collagen	en
dc.subject	fibroblast	en
dc.subject	JNK	en
dc.subject	p38	en
dc.subject	PDE IV	en
dc.subject	TGF-ß	en
dc.subject.ddc	610
dc.title	Anti-fibrotic Effects of ONO-EF-345, a Specific Phosphodiesterase IV inhibitor, on 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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