Interacting monocytes and synoviocytes induce adhesion molecules by a cytokine-regulated process.
Monocytes/macrophages and synovial fibroblast-like cells are in intimate contact in the synovium and are believed to play a critical role in the development of rheumatoid arthritis. We investigated the effects of monocyte-synoviocyte interactions in vitro on cytokine release and the expression of adhesion molecules. Using a sensitive Western blot assay, we found that VCAM-1 and ICAM-1 expression were up-regulated in synoviocytes following coculture. The interaction also resulted in the accumulation of TNF and IL-6, but not IFN-gamma in the culture medium. Culture supernatant from monocyte-synoviocyte samples effectively induced adhesion molecules in synoviocytes. Anti-TNF partially inhibited the increase in VCAM-1 and ICAM-1 expression, indicating that TNF in part mediates VCAM-1 and ICAM-1 expression. Interestingly, the induction of cytokines and adhesion molecules did not require cell contact between monocytes and synoviocytes, suggesting cell communication via soluble factors. T cell cytokines enhanced the induction of adhesion molecules induced by the monocyte-synoviocyte interaction. IFN-gamma and IL-4, which are produced by distinct T helper subsets, had differential effects on monocyte-synoviocyte interactions. IFN-gamma had a minimal effect on VCAM-1 expression by synovial fibroblasts, but synergized with monocytes to dramatically up-regulate ICAM-1 expression. IL-4 had no effect on ICAM-1 expression but enhanced monocyte-induced expression of VCAM-1. Our results demonstrate that the up-regulation of adhesion molecules following monocyte-synoviocyte interactions is mediated by soluble factors and can be regulated by specific T cell cytokines.
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Institute for Inflammation and Autoimmunity, Miles Research Center, West Haven, CT 06516.
Conrad
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Webb
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Sarr
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Macaro
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D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000503:physiopathology; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002450:Cell Communication; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors; D009000:Monocytes / Q000502:physiology*; D013583:Synovial Membrane / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D007371:Interferon-gamma