The single feature most characteristic of rheumatoid arthritis is tumorlike proliferation of the synovium. Transformed-appearing fibroblastlike cells and new blood vessels are the major proliferating cell populations. During the past year, we have obtained additional evidence that platelet-derived growth factor, particularly a PDGF-B-like polypeptide, plays a role in regulating the growth and function of the fibroblast-like cells in diseased synovium. We have shown that its production correlates with expression of acidic fibroblast growth factor, or heparin binding growth factor-1, in rheumatoid synovial tissues. These growth factors probably synergistically stimulate the tumorlike proliferation of rheumatoid synovium. We have continued studies of the regulation of collagenase and transin/stromelysin transcription by interleukin-1 in rheumatoid synovial fibroblasts. We have provided evidence that collagenase transcription is regulated through a cis regulatory element, the TRE, and the transactivating factors, c-jun and c-fos, which together comprise the AP-1 element. Retinoid suppression of collagenase transcription is mediated through inhibition of c-fos transcription. We have shown that IL-1 regulation of stromelysin involves two antagonistic pathways, an inhibitory, cAMP-dependent and stimulatory, protein kinase C-dependent pathway.
