Effects of nitric oxide on matrix metalloproteinase-2 production by rheumatoid synovial cells
Effects of nitric oxide on matrix metalloproteinase-2 production by rheumatoid synovial cells
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DOI：
10.1016/s0024-3205(00)00998-x
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发表时间：
2001-01-12
期刊：
影响因子：
6.1
通讯作者：
Eguchi, K
中科院分区：
文献类型：
--
作者：
Hirai, Y;Migita, K;Eguchi, K
一氧化氮（NO）是一种由l -精氨酸通过包括一氧化氮合酶（NOS）在内的一系列酶产生的多功能信使分子。本研究旨在研究NO是否调节类风湿性滑膜细胞中基质金属蛋白酶（MMPs）的产生，MMPs可降解细胞外基质（ECM）的所有成分。我们研究了由NO供体s -亚硝基-n -乙酰- dl -青霉胺（SNAP）外源性产生的NO对类风湿滑膜细胞产生MMPs的影响。用snap处理的滑膜细胞培养培养基，用明胶酶谱法和免疫印迹法检测。用SNAP孵育滑膜细胞导致明胶酶A以剂量依赖的方式产生。此外，RT-PCR分析显示，snap处理的滑膜细胞诱导MMP-2 mRNA表达。相反，SNAP不影响类风湿性滑膜细胞优先抑制MMP-2的TIMP-1和TIMP-2的产生。我们的数据表明NO可以调节类风湿滑膜细胞产生MMP，因此有助于类风湿关节炎关节成分的ECM降解。(C) 2001爱思唯尔科学公司版权所有。
Nitric oxide (NO) is a multifunctional messenger molecule generated from L-arginine by a family of enzymes, including nitric oxide synthase (NOS). This study was performed to examine whether NO modulates the production of matrix metalloproteinases (MMPs), which degrade all components of extracellular matrix (ECM), in rheumatoid synovial cells. We investigated the effects of exogenously generated NO by a NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), on the MMPs production by rheumatoid synovial cells. Culture media conditioned by SNAP-treated synovial cells were examined by gelatin zymography and immunoblot analysis. Incubation of synovial cells with SNAP resulted in gelatinase A production in a dose-dependent fashion. Furthermore, RT-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 synovial cells. Our data indicate that NO could modulate MMP production by rheumatoid synovial cells and therefore contribute to ECM degradation of articular components in RA. (C) 2001 Elsevier Science Inc. All rights reserved.