Interacting monocytes and synoviocytes induce adhesion molecules by a cytokine-regulated process

• Published in: Lymphokine and cytokine research Vol. 12; no. 4; p. 213
• Main Authors: Blue, M L, Conrad, P, Webb, D L, Sarr, T, Macaro, M
• Format: Journal Article
• Language: English
• Published: United States 01.08.1993
• Subjects: Antigens, CD - analysis; Antigens, Differentiation, Myelomonocytic - analysis; Arthritis, Rheumatoid - physiopathology; Blotting, Western; Cell Adhesion Molecules - biosynthesis; Cell Communication; Cells, Cultured; Cytokines - biosynthesis; Endothelium, Vascular - physiology; Fibroblasts - metabolism; Fibroblasts - physiology; Flow Cytometry; Humans; Intercellular Adhesion Molecule-1; Interferon-gamma - biosynthesis; Interferon-gamma - pharmacology; Interleukin-1 - biosynthesis; Interleukin-4 - pharmacology; Interleukin-6 - biosynthesis; Lipopolysaccharide Receptors; Monocytes - physiology; Synovial Membrane - drug effects; Synovial Membrane - physiology; Synovial Membrane - physiopathology; T-Lymphocytes - immunology; T-Lymphocytes - physiology; Vascular Cell Adhesion Molecule-1
• ISSN: 1056-5477

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.