NITRIC-OXIDE MEDIATES SUPPRESSION OF CARTILAGE PROTEOGLYCAN SYNTHESIS BY INTERLEUKIN-1
NITRIC-OXIDE MEDIATES SUPPRESSION OF CARTILAGE PROTEOGLYCAN SYNTHESIS BY INTERLEUKIN-1
复制标题
DOI：
10.1006/bbrc.1994.1426
复制
发表时间：
1994-04-15
影响因子：
3.1
通讯作者：
EVANS, C
中科院分区：
文献类型：
--
作者：
TASKIRAN, D;STEFANOVICRACIC, M;EVANS, C
兔关节软骨切片在暴露于人重组白细胞介素-1 β（hrIL-1 β）或兔滑膜细胞因子（CAF）后合成大量的一氧化氮（NO）。这些刺激物中的每一种也强烈抑制（SO 42-）-S-35生物合成掺入软骨蛋白聚糖的糖胺聚糖（GAG）中。用NO合酶的竞争性抑制剂L-N-G-单甲基精氨酸（L-NMA）处理软骨碎片，既抑制了响应于IL-1和CAF的NO合成，又恢复了蛋白多糖的合成。D-NMA在这方面无活性，L-精氨酸逆转L-NMA的作用。NO的有机供体S-亚硝基乙酰青霉胺（SNAP）可逆地模拟了IL-1和CAF对（SO_（42-））-S-35掺入的影响。这些数据表明，内源性合成的NO是介体，其减少软骨蛋白多糖的合成响应于细胞因子，如IL-1和CAF。NO产生的拮抗剂可以促进软骨基质的合成，因此具有作为软骨保护剂或软骨修复剂的潜力。(C)1994年出版社出版。
Slices of rabbit articular cartilage synthesized large quantities of nitric oxide (NO) following exposure to human recombinant interleukin-1 beta (hrIL-1 beta) or rabbit synovial cytokines (CAF). Each of these stimuli also strongly suppressed the biosynthetic incorporation of (SO42-)-S-35 into the glycosaminoglycans (GAGs) of cartilage proteoglycans. Treatment of cartilage fragments with L-N-G-monomethylarginine (L-NMA), a competitive inhibitor of NO synthase, both inhibited NO synthesis in response to IL-1 and CAF and restored proteoglycan synthesis. D-NMA was inactive in this regard, and L-arginine reversed the effects of L-NMA. S-nitrosylacetylpenicillamine (SNAP), an organic donor of NO, reversibly mimicked the effect of IL-1 and CAF on (SO42-)-S-35 incorporation. These data suggest that endogenously synthesized NO is the mediator which reduces cartilage proteoglycan synthesis in response to cytokines such as IL-1 and CAF. Antagonists of NO production may promote cartilage matrix synthesis and thus have potential as chondroprotective or chondroreparative agents. (C) 1994 Academic Press, Inc.