Cytokines in chronic inflammatory arthritis. VI. Analysis of the synovial cells involved in granulocyte-macrophage colony-stimulating factor production and gene expression in rheumatoid arthritis and its regulation by IL-1 and tumor necrosis factor-alpha.

作者: G S Firestein , N J Zvaifler , C B Brown , K Kaushansky , J M Alvaro-Gracia

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摘要: Granulocyte-macrophage CSF (GM-CSF) is a potent stimulator of macrophages and neutrophils produced by rheumatoid arthritis (RA) synovium. We now report studies that identify some the synovial cells cytokines responsible for local GM-CSF production gene expression in RA. was assayed ELISA supernatants from cultured RA fibroblast-like synoviocytes stimulated with various (IL-1 beta, TNF-alpha, macrophage-CSF, IFN-gamma, IL-6, TGF-beta). Immunoreactive detected IL-1 beta TNF-alpha-stimulated cultures, but not medium or any other cytokines. TNF-alpha had synergistic effect on production. analyzed ribonuclease protection assay, Northern blot analysis, situ hybridization. Both induced mRNA accumulation, maximum after 4 h stimulation. then studied macrophage-like (MLS) isolated fresh specimens flow microfluorimetry. Fresh MLS spontaneously secreted cytokine exogenous no effect. After 1 wk culture, additional stimulation required Finally, hybridization performed freshly subpopulations cells, identified RNA transcripts MLS.

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