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

J. Biol. Chem., Vol. 278, Issue 5, 2903-2912, January 31, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/5/2903    most recent M110773200v1 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 Legendre, F. Articles by Bogdanowicz, P. Search for Related Content PubMed PubMed Citation Articles by Legendre, F. Articles by Bogdanowicz, P. Social Bookmarking                      What's this?

JAK/STAT but Not ERK1/ERK2 Pathway Mediates Interleukin (IL)-6/Soluble IL-6R Down-regulation of Type II Collagen, Aggrecan Core, and Link Protein Transcription in Articular Chondrocytes
ASSOCIATION WITH A DOWN-REGULATION OF SOX9 EXPRESSION^*

Florence Legendre^§, Jayesh Dudhia^¶, Jean-Pierre Pujol, and Patrick Bogdanowicz

From the  Laboratoire de Biochimie du Tissu Conjonctif, Faculté de Médecine, 14032 Caen Cedex, France and the ^¶ Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 OTU, United Kingdom

Signal transducers and activators of transcription (STAT) factors are cytoplasmic proteins that can be activated by Janus kinases (JAK) and that modulate gene expression in response to cytokine receptor stimulation. STAT proteins dimerize, translocate into the nucleus, and activate specific target genes. In the present study, we show for the first time that interleukin-6 (IL), in the presence of its soluble receptor (sIL-6R), induces activation of JAK1, JAK2, and STAT1/STAT3 proteins in bovine articular chondrocytes. Western blotting and mobility shift assays demonstrated that this effect is accompanied by the DNA binding of the STAT proteins. The mitogen-activated protein kinase pathway was also activated in response to IL-6/sIL-6R association, as reflected by phosphorylation of ERK1 and ERK2 proteins. In these conditions, the expression of cartilage-specific matrix genes, type II collagen, aggrecan core, and link proteins was found to be markedly down-regulated. This negative effect was abolished by addition of parthenolide, an inhibitor of the STAT activation, whereas blockade of the MAP kinases with PD098059 was without significant effect. Thus, activation of the STAT signaling pathways, but not ERK-dependent pathways, is essential for down-regulation of the major cartilage-specific matrix genes by IL-6. In addition, a parallel reduction of Sox9 expression, a key factor of chondrocyte phenotype, was found in these experimental conditions. These IL-6 effects might contribute to the phenotype loss of chondrocytes in joint diseases and the alteration of articular cartilage associated with this pathology.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				B. Poree, M. Kypriotou, C. Chadjichristos, G. Beauchef, E. Renard, F. Legendre, M. Melin, S. Gueret, D.-J. Hartmann, F. Mallein-Gerin, et al. Interleukin-6 (IL-6) and/or Soluble IL-6 Receptor Down-regulation of Human Type II Collagen Gene Expression in Articular Chondrocytes Requires a Decrease of Sp1{middle dot}Sp3 Ratio and of the Binding Activity of Both Factors to the COL2A1 Promoter J. Biol. Chem., February 22, 2008; 283(8): 4850 - 4865. [Abstract] [Full Text] [PDF]

				Y. Li, G. Takemura, H. Okada, S. Miyata, R. Maruyama, L. Li, M. Higuchi, S. Minatoguchi, T. Fujiwara, and H. Fujiwara Reduction of inflammatory cytokine expression and oxidative damage by erythropoietin in chronic heart failure Cardiovasc Res, September 1, 2006; 71(4): 684 - 694. [Abstract] [Full Text] [PDF]

				O. Lopez-Franco, P. Hernandez-Vargas, G. Ortiz-Munoz, G. Sanjuan, Y. Suzuki, L. Ortega, J. Blanco, J. Egido, and C. Gomez-Guerrero Parthenolide Modulates the NF-{kappa}B-Mediated Inflammatory Responses in Experimental Atherosclerosis Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1864 - 1870. [Abstract] [Full Text] [PDF]

				P. Allavena, M. Signorelli, M. Chieppa, E. Erba, G. Bianchi, F. Marchesi, C. O. Olimpio, C. Bonardi, A. Garbi, A. Lissoni, et al. Anti-inflammatory Properties of the Novel Antitumor Agent Yondelis (Trabectedin): Inhibition of Macrophage Differentiation and Cytokine Production Cancer Res., April 1, 2005; 65(7): 2964 - 2971. [Abstract] [Full Text] [PDF]