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.