HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 40, 41783-41791, October 1, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/40/41783    most recent M406951200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jinnin, M. Articles by Tamaki, K. Search for Related Content PubMed PubMed Citation Articles by Jinnin, M. Articles by Tamaki, K. Social Bookmarking                      What's this?

Interleukin-13 Stimulates the Transcription of the Human 2(I) Collagen Gene in Human Dermal Fibroblasts^*

Masatoshi Jinnin, Hironobu Ihn, Kenichi Yamane, and Kunihiko Tamaki

From the Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan

Interleukin (IL)-13 is a novel lymphokine produced by activated Type 2 helper cells. In this study, we examined the target genes of IL-13 by the cDNA microarray analysis in human dermal fibroblasts. We focused on the human 2(I) collagen gene, which was one of the IL-13-induced genes by the microarray analysis. IL-13 induced type I collagen protein as well as mRNA in a dose-dependent manner. Actinomycin D, an RNA synthesis inhibitor, significantly blocked the IL-13-mediated up-regulation of 2(I) collagen mRNA expression, whereas cycloheximide, a protein synthesis inhibitor, did not block this up-regulation. In addition, IL-13 treatment induced the promoter activity of 2(I) collagen by nuclear run-on transcription assay and chloramphenicol acetyltransferase assay. IL-13-mediated transcriptional activation of 2(I) collagen gene or type I collagen protein up-regulation was inhibited by the treatment of fibroblasts with a selective phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or STAT6 antisense oligonucleotide, but not by PD98059, a specific inhibitor of MEK/ERK, or SB202190 or SB203580, specific inhibitors of p38 MAPK; IL-13 induced the phosphorylation of PI3K p85 regulatory subunit and STAT6. These results suggest that IL-13 may play a role in the regulation of extracellular matrix and indicate the possible therapeutic value of the blockade of IL-13 signaling pathways via PI3K and STAT6 in fibrosis.

Received for publication, June 22, 2004

^* This work is supported in part by a grant for scientific research from Japanese Ministry of Education and by project research for progressive systemic sclerosis from the Japanese Ministry of Health and Welfare. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

These authors contributed equally to this work.

To whom correspondence should be addressed. Tel.: 81-3-5800-8661; Fax: 81-3-3814-1503; E-mail: IN-DER{at}h.u-tokyo.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. Y. Leung, D. Tian, C. P. Brangwynne, D. A. Weitz, and D. J. Tschumperlin A new microrheometric approach reveals individual and cooperative roles for TGF-{beta}1 and IL-1{beta} in fibroblast-mediated stiffening of collagen gels FASEB J, July 1, 2007; 21(9): 2064 - 2073. [Abstract] [Full Text] [PDF]

				C. J. Scotton, F. O. Martinez, M. J. Smelt, M. Sironi, M. Locati, A. Mantovani, and S. Sozzani Transcriptional Profiling Reveals Complex Regulation of the Monocyte IL-1{beta} System by IL-13 J. Immunol., January 15, 2005; 174(2): 834 - 845. [Abstract] [Full Text] [PDF]