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  • Title: Rheumatoid synovial fibroblasts are stimulated by the cellular adhesion to T cells through lymphocyte function associated antigen-1/intercellular adhesion molecule-1.
    Author: Nakatsuka K, Tanaka Y, Hubscher S, Abe M, Wake A, Saito K, Morimoto I, Eto S.
    Journal: J Rheumatol; 1997 Mar; 24(3):458-64. PubMed ID: 9058649.
    Abstract:
    OBJECTIVE: To determine if T cells stimulate synovial fibroblasts to produce inflammatory cytokines through cellular adhesion in synovitis of rheumatoid arthritis (RA). METHODS: Immunohistochemical staining, flow microfluorometry, adhesion assay, ELISA, and Northern blot analysis to determine production of interleukin-1beta (IL-1beta) from RA synovium and RA synovial fibroblast-like cell line. RESULTS: We observed the following novel features of cellular adhesion of T cells to synovial fibroblasts, which suggest a role for induction of cytokine production in synovial fibroblasts: (a) CD11a (lymphocyte function associated antigen-1 alpha) positive T cells accumulated around CD54 [intercellular adhesion molecule (ICAM-1)] positive synoviocytes in active RA synovium, shown by immunohistochemical studies: (b) synovial fibroblastic cell line E11 expressed a single adhesion molecule ICAM-1, the expression of which was not affected by IL-1beta; (c) E11 adhered to phorbol myristate acetate (PMA) activated T cells within 30 min, not resting T cells, and its adhesion was completely inhibited by anti-LFA-1 monoclonal antibody (Mab); (d) pretreatment of E11 with IL-1beta did not affect the adhesion of E11 to PMA activated T cells; (e) IL-1beta production and IL-1beta mRNA transcription from E11 were induced by the addition of T cells in a cell number dependent manner and the induced production and transcription were inhibited by anti-LFA-1 Mab. CONCLUSION: T cells infiltrating the synovium may play a pivotal role in the pathogenesis of RA, by inducing IL-1beta production of synovial fibroblasts by sequential events, namely, T cell-synoviocyte cellular adhesion through LFA-1/ICAM-1, signal transduction, and production of IL-1beta induced by the cellular adhesion.
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