Expression of interleukin-18 receptor in fibroblast-like synoviocytes.
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 alpha-chain and beta-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.
Möller
Burkhard
B
Rheumazentrum Rhein-Main, Marienburgstrasse 2, D-60528 Frankfurt, Germany. B.Moeller@em.uni-frankfurt.de
Kessler
Uta
U
Rehart
Stefan
S
Kalina
Uwe
U
Ottmann
Oliver G
OG
Kaltwasser
Joachim Peter
JP
Hoelzer
Dieter
D
Kukoc-Zivojnov
Natasa
N
D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism / Q000494:pharmacology; D053727:Interleukin-18 Receptor alpha Subunit; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D053724:Receptors, Interleukin-18; D015398:Signal Transduction; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020298:U937 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D017077:Culture Media, Conditioned; C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D017364:Collagenases; D019278:Matrix Metalloproteinase 3; D015232:Dinoprostone