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Open Access Research article

Expression of interleukin-18 receptor in fibroblast-like synoviocytes

Burkhard Möller1*, Uta Kessler2, Stefan Rehart3, Uwe Kalina2, Oliver G Ottmann2, Joachim Peter Kaltwasser2, Dieter Hoelzer2 and Natasa Kukoc-Zivojnov2

Author Affiliations

1 Rheumazentrum Rhein-Main, Frankfurt, Germany

2 Universitätsklinikum, Medizinische Klinik III, Frankfurt, Germany

3 Orthopädische Universitätsklinik, Abteilung für Rheumaorthopädie, Frankfurt, Germany

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Arthritis Res 2002, 4:139-144  doi:10.1186/ar390

Published: 14 November 2001

Abstract

An excess of the proinflammatory substance IL-18 is present in joints of patients with rheumatoid arthritis (RA), and expression of IL-18 receptor (IL-18R) regulates IL-18 bioactivity in various cell types. We examined the expression of IL-18R α-chain and β-chain and the biologic effects of IL-18 in fibroblast-like synoviocytes (FLS) after long-term culture. The presence of both IL-18R chains was a prerequisite for IL-18 signal transduction in FLS. However, all FLS cultures studied were either resistant or barely responsive to IL-18 stimulation as regards cell proliferation, expression of adhesion molecules ICAM-1 and vascular cell adhesion molecule (VCAM)-1, and the release of interstitial collagenase and stromelysin, IL-6 and IL-8, prostaglandin E2, or nitric oxide. We conclude that the presence of macrophages or IL-18R+ T cells that can respond directly to IL-18 is essential for the proinflammatory effects of IL-18 in synovitis in RA.

Keywords:
fibroblast; interleukin-18; receptor; rheumatoid arthritis; synoviocyte