Expression of interleukin-18 receptor in fibroblast-like synoviocytes.docVIP

Available online /content/4/2/139 Research article Expression of interleukin-18 receptor in fibroblast-like synoviocytes Burkhard M?ller*, Uta Kessler?, Stefan Rehart?, Uwe Kalina?, Oliver G Ottmann?, Joachim Peter Kaltwasser?, Dieter Hoelzer? and Natasa Kukoc-Zivojnov? *Rheumazentrum Rhein-Main, Frankfurt, Germany ?Universit?tsklinikum, Medizinische Klinik III, Frankfurt, Germany ?Orthop?dische Universit?tsklinik, Abteilung für Rheumaorthop?die, Frankfurt, Germany Correspondence: Burkhard M?ller, Rheumazentrum Rhein-Main, Marienburgstra?e 2, D-60528 Frankfurt, Germany. Tel: +49 69 6705 279; fax: +49 69 6705 393; e-mail: B.Moeller@em.uni-frankfurt.de Received: 12 December 2000 Revisions requested: 17 January 2001 Revisions received: 31 October 2001 Accepted: 31 October 2001 Arthritis Res 2002, 4:139-144 This article may contain supplementary data which can only be found online at /content/4/2/139 ? 2002 M?ller et al., licensee BioMed Central Ltd Published: 14 November 2001 (Print ISSN 1465-9905; Online ISSN 1465-9913) 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 E , or nitric oxide. We conclude that the 2 presence of macrophages or IL-18R+ T cells that can respond directly to IL-18 is essential