Effects of nitric oxide on matrix metalloproteinase-2 production by rheumatoid synovial cells

Nitric oxide (NO) is a multifunctional messenger molecule generated from L- arginine by a family of enzymes, including nitric oxide synthase (NOS). Thi s study was performed to examine whether NO modulates the production of mat rix metalloproteinases (MMPs), which degrade all components of extracellula r matrix (ECM), in rheumatoid synovial cells. We investigated the effects o f exogenously generated NO by a NO donor, S-nitroso-N-acetyl-DL-penicillami ne (SNAP), on the MMPs production by rheumatoid synovial cells. Culture med ia conditioned by SNAP-treated synovial cells were examined by gelatin zymo graphy and immunoblot analysis. Incubation of synovial cells with SNAP resu lted in gelatinase A production in a dose-dependent fashion. Furthermore, R T-PCR analysis demonstrated that MMP-2 mRNA expression was induced in SNAP- treated synovial cells. In contrast, SNAP did not influence the production of TIMP-1 and TIMP-2, which preferentially inhibit MMP-2, by rheumatoid syn ovial cells. Our data indicate that NO could modulate MMP production by rhe umatoid synovial cells and therefore contribute to ECM degradation of artic ular components in RA. (C) 2001 Elsevier Science Inc. All rights reserved.