EFFECTS OF LIPID PEROXIDE ON PRODUCTION OF MATRIX METALLOPROTEINASE-1(TISSUE COLLAGENASE) AND METALLOPROTEINASE-3 (STROMELYSIN) AND TISSUEINHIBITOR METALLOPROTEINASE-1 BY HUMAN RHEUMATOID SYNOVIAL FIBROBLASTS

The effects of linoleic acid hydroperoxide on the production of matrix metalloproteinases (MMPs) including MMP-1 (tissue collagenase), -2 (' 'type IV collagenase''), and -3 (stromelysin) and of tissue inhibitor of metalloproteinase 1 (TIMP-1), as well as DNA synthesis were investi gated in rheumatoid synovial fibroblasts. Our results demonstrated tha t the levels of proMMP-1 and -3 and TIMP-1 were extremely elevated whe n 0.5-2.0 nmole/ml of linoleic acid hydroperoxide was added to culture s of rheumatoid synovial fibroblasts. DNA synthesis, however, was inhi bited by linoleic acid hydroperoxide. These results indicate that lipi d peroxide causes the disruption of extracellular matrix macromolecule s and the inhibition of cell repair in synovial tissue. Therefore, the y also suggest that an elevated level of oxygen free radical and/or li pid peroxides in synovial fluid may play an important role in the proc ess of rheumatoid arthritis, resulting in the disruption of the joint. (C) 1993 Academic Press, Inc.