SUSTAINED AND DISTINCTIVE PATTERNS OF GENE ACTIVATION IN SYNOVIAL FIBROBLASTS AND WHOLE SYNOVIAL TISSUE OBTAINED FROM INFLAMMATORY SYNOVITIS

Fibroblastoid synovial lining cells isolated from rheumatoid and other chronic inflammatory synovial tissue exhibit distinctive and sustaine d alterations in serial culture not commonly found in similarly cultur ed cells from osteoarthritic synovium. These are demonstrable using a multi-gene dot blot assay by labelling reverse transcribed fibroblast cDNA which is hybridized to plasmids containing relevant target gene i nserts. Cultured synovial fibroblastoid cells from patients with chron ic inflammatory synovitis expressed significantly higher levels of str omelysin, vimentin and TIMP-1 mRNA and lower levels of c-myc compared to cells isolated from osteoarthritis synovium although with considera ble variation. Early fetal synovial lining cells were similar to cells from osteoarthritis synovium but vimentin expression was higher. Mark ed differences in patterns of gene expression between cell lines persi sted through 10 serial passages over 6-8 months. In whole synovia, the average level of mRNA for stromelysin, vimentin, IL-4, IL-6, TIMP-1, cathepsin D, gelatinase, TGF alpha, c-fms and DR beta were preferentia lly expressed in inflammatory tissue while c-myc expression was higher in osteoarthritis synovium. Inflammatory synovium also expressed TNF alpha, IL-1 alpha, IL-1 beta, IL-2, c-sis, tissue plasminogen activato r, CSF-1, and GM-CSF. This pattern resembles, in part, that found in c ultured inflammatory fibroblasts but, in addition, gene products appar ently reflecting the presence of activated monocytes and lymphocytes w ere detected. These results provide evidence that profiles of certain gene activation in cells from patients with inflammatory synovitis dif fer from those with non-inflammatory disease and suggest that the fibr oblastoid cells are responsible for a considerable proportion of the a ltered phenotypic expression pattern in whole tissue. Furthermore, thi s modulated pattern of gene activation appears to be an intrinsic pro- inflammatory characteristic of the fibroblastoid cells initiated in re sponse to chronic inflammation and persists for a prolonged period in the absence of other inflammatory cells.