Open AccessImbalance between interstitial collagenase and tissue inhibitor of metalloproteinases 1 in synoviocytes and fibroblasts upon direct contact with stimulated T lymphocytes: Involvement of membrane‐associated cytokines
Author(s) -
Burger Danielle,
Rezzonico Roger,
Li JianMei,
Modoux Christine,
Pierce Richard A.,
Welgus Howard G.,
Dayer JeanMichel
Publication year - 1998
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(199810)41:10<1748::aid-art7>3.0.co;2-3
Subject(s) - fibroblast , matrix metalloproteinase , synovial membrane , interstitial collagenase , collagenase , prostaglandin e2 , microbiology and biotechnology , cell culture , tissue inhibitor of metalloproteinase , dermal fibroblast , t cell , chemistry , cytokine , cell , inflammation , biology , immunology , endocrinology , immune system , biochemistry , enzyme , genetics
Objective To determine whether direct cell‐cell contact with stimulated T lymphocytes (a) differentially modulates the production of interstitial collagenase (matrix metalloproteinase 1 [MMP‐1]) and tissue inhibitor of metalloproteinases 1 (TIMP‐1) on human synoviocytes and dermal fibroblasts, and (b) induces the production of prostaglandin E 2 (PGE 2 ); and to identify the membrane‐associated factors on T cell surfaces involved in these mechanisms. Methods Dermal fibroblasts and fibroblast‐like synovial cells (synoviocytes) were cultured with fixed T cells, isolated plasma membranes from T cells, interleukin‐1β (IL‐1β; 250 pg/ml), or transforming growth factor β (TGFβ; 5 ng/ml). Culture supernatants were assayed for the production of MMP‐1, TIMP‐1, and PGE 2 . The expression of MMP‐1 and TIMP‐1 messenger RNA was analyzed by Northern blot of total fibroblast RNA. Results Membranes of stimulated T cells, i.e., human peripheral blood T lymphocytes (PBTL) and the human T cell line HUT‐78, induced the production of PGE 2 and MMP‐1 on both synoviocytes and dermal fibroblasts. TIMP‐1 production was enhanced upon contact with PBTL stimulated for short periods of time (2‐4 hours) but not for longer periods. Similar results were obtained with CD4+ and CD8+ synovial tissue T cell clones (TCCs), which induced the production of TIMP‐1 by fibroblasts when stimulated for short (2‐4 hours), but not long, periods of time. This time dependency was not observed with HUT‐78 cells. The production of MMP‐1 by fibroblasts and synoviocytes upon cellular contact with stimulated T cells was higher than that induced by an optimum concentration of IL‐1β, whereas the production of PGE 2 was equivalent or slightly lower. Cell membrane‐associated IL‐1α and tumor necrosis factor α, but not CD69, CD40 ligand, or CD11b, were involved in the induction of MMP‐1 and PGE 2 production, as shown by blockade experiments using monoclonal antibodies and cytokine antagonists. Conclusion Synovial tissue TCCs and PBTL stimulated for long periods of time trigger the production of PGE 2 and MMP‐1, but not TIMP‐1, in synoviocytes and dermal fibroblasts, thus inducing an imbalance between the metalloenzyme and its inhibitor. These results demonstrate that T cells may affect fibroblast and synoviocyte functions directly (i.e., by contact activation) and indirectly (i.e., by activation of cytokine production in monocyte/macrophages, which in turn, trigger stromal cell functions). Since the production of MMPs in monocyte/macrophages is also induced upon contact with stimulated T cells, our results strongly suggest that contact of synovial cells with chronically stimulated T lymphocytes favors matrix catabolism. By analogy, this mechanism may trigger tissue destruction in vivo and, thus, may potentiate tissue destruction in chronic inflammatory diseases such as RA.