TNF-ALPHA INDUCES THE TRANSCRIPTION FACTOR EGR-1, PRO-INFLAMMATORY CYTOKINES AND CELL-PROLIFERATION IN HUMAN SKIN FIBROBLASTS AND SYNOVIAL LINING CELLS

In rheumatoid arthritis (RA) cell proliferation and altered metallopro teinase expression of synovial lining cells are associated with increa sed levels of TNF-alpha in the rheumatoid joint. We previously showed that synoviocytes of RA patients express high levels of the transcript ion factor Egr-1. Here we report that TNF-alpha is capable of inducing high Egr-1 mRNA levels in human skin fibroblasts and in synoviocytes from both, RA and reactive arthritis patients. Moreover, we observed i n vitro a marked increase in fibroblast proliferation, a loss of growt h inhibition by cell-to-cell contact with pannus-like cell growth and an altered cytokine expression pattern when synoviocytes were cultured in presence of TNF-alpha.