Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

This article is part of the supplement: 6th Global Arthritis Research Network (GARN) Meeting

Open Badges Poster presentation

Activation of synovial fibroblasts by laminin-1 and transforming growth factor beta induces expression of stromelysins independently of TNFα, IL-1β or NF-κB

Katrin Warstat1, Thomas Pap2, Gerd Klein3, Steffen Gay4 and Wilhelm K Aicher1

Author Affiliations

1 Center for Medical Research (ZMF), Department of Orthopedic Surgery, Eberhard-Karls-University Medical School, Tübingen, Germany

2 Division of Molecular Medicine of Musculoskeletal Tissue, Department of Orthopedics, Münster University Hospital, Münster, Germany

3 Center for Medical Research (ZMF), Section for Transplantation Immunology, University of Tübingen, Tübingen, Germany

4 WHO Center for Experimental Rheumatology, University Hospital Zürich, Zürich, Switzerland

For all author emails, please log on.

Arthritis Research & Therapy 2007, 9(Suppl 3):P17  doi:10.1186/ar2243

The electronic version of this article is the complete one and can be found online at:

Published:19 October 2007

© 2007 BioMed Central Ltd

Poster presentation

Recently it was shown that attachment of synovial fibroblasts (SF) from rheumatoid arthritis patients to laminin-111 (LM-111) induced an elevated expression of stromelysin-1 (MMP-3). We therefore investigated the regulation of additional matrix metalloproteinases (MMPs) and their specific tissue inhibitors of matrix metalloproteinases (TIMPs) by attachment to LM-111 in the presence of transforming growth factor beta (TGFβ). Changes in steady-state mRNA levels encoding TIMPs and MMPs were investigated by quantitative RT-PCR. Production of MMPs and cytokines was monitored by a multiplexed immunoarray or by ELISA. Signal transduction pathways were studied by immunoblotting. Attachment of SF to LM-111 in the presence of TGFβ induced significant increases in stromelysin-1 mRNA (12.35-fold, P < 0.001) and protein (mean 62 ng/ml, sixfold, P < 0.008). Expression of stromelysin-2 (MMP-10) mRNA (11.68-fold, P < 0.05) and protein (54 ng/ml, 20-fold, P ≥ 0.02) was significantly activated as well. All other TIMPs and MMPs investigated failed to show this LM-111-facilitated TGFβ response. Induction of stromelysin-1 and stromelysin-2 was associated with the activation of transcription factors c-fos and Egr-1, but phosphorylation of NF-κB was not observed. Further, LM-111-activated and TGFβ-activated SF failed to produce remarkable amounts of IL-1β or TNFα. We conclude that costimulation of synovial fibroblasts by LM-111 together with TGFβ suffices to induce significant expression of MMP-3 and MMP-10 by SF and that this induction is independent of phosphorylation of NF-κB.