Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide.
Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide.
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DOI：
10.4049/jimmunol.147.11.3915
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发表时间：
1991-12
影响因子：
4.4
通讯作者：
J. Stadler;M. Stefanovic‐Racic;T. Billiar;R. D. Curran;L. McIntyre;H. Georgescu;R. L. Simmons;C. Evans
中科院分区：
文献类型：
--
作者：
J. Stadler;M. Stefanovic‐Racic;T. Billiar;R. D. Curran;L. McIntyre;H. Georgescu;R. L. Simmons;C. Evans
尽管IL-1是软骨细胞代谢的重要调节因子，但由IL-1触发的受体后事件仍不清楚。本研究表明，IL-1可诱导关节软骨细胞合成一氧化氮(N=O)。内毒素也能诱导N=O的合成。其他炎症介质，如干扰素-γ、成纤维细胞生长因子和肿瘤坏死因子-α，不能刺激.N=O的产生，但它们增加了IL-1的效力。IL-1、内毒素和肿瘤坏死因子-α联合作用可诱导355+/-51nmol/10(6)细胞/72小时亚硝酸盐(NO2-)的最大产生，亚硝酸盐是N=O生成的稳定终产物。.N=O的生物合成需要大约6小时的诱导期，持续至少72小时。竞争性抑制剂NG-单甲基-L-精氨酸抑制.N=O的合成会导致单独用IL-1激活的软骨细胞抑制明胶酶和前列腺素E_2的合成。相反，在IL-1、内毒素和肿瘤坏死因子-α的联合作用下，NMA可促进明胶酶和前列腺素E_2的合成。当两种刺激剂联合应用时，前列腺素E_2合成由42.0+/-21.0增加到174.0+/-33.5 ng/10(6)细胞/72h。IL-1和成纤维细胞生长因子刺激的软骨细胞暴露于真正的外源性.N=O后，PGE2合成在1小时内从未处理细胞的5.6+/-1.7增加到15.8+/-6.8 ng/10(6)处理细胞，随后在接下来的2小时内PGE2合成受到抑制。
Although IL-1 is an important modulator of chondrocyte metabolism, the postreceptor events triggered by IL-1 remain obscure. The present study shows that IL-1 induces the biosynthesis of nitric oxide (.N = O) by articular chondrocytes. Synthesis of .N = O is also induced by LPS. Other inflammatory mediators such as IFN-gamma, fibroblast growth factor, and TNF-alpha fail to provoke the production of .N = O, but they increase the potency of IL-1. A combination of IL-1, LPS, and TNF-alpha was shown to induce maximal production of 355 +/- 51 nmol/10(6) cells/72 h of nitrite (NO2-), which was measured as a stable end-product of .N = O generation. The biosynthesis of .N = O requires an induction period of approximately 6 h and continues for at least 72 h. Inhibition of .N = O production with the competitive inhibitor NG-monomethyl-L-arginine (NMA) leads to a suppression of gelatinase and PGE2 synthesis by chondrocytes activated with IL-1 alone. In contrast, NMA enhances the synthesis of both gelatinase and PGE2 after activation with a combination of IL-1, LPS, and TNF-alpha. An increase of PGE2 synthesis from 42.0 +/- 21.0 to 174.0 +/- 33.5 ng/10(6) cells/72 h resulted from the addition of NMA when these stimulatory agents were combined. Exposure of IL-1 and fibroblast growth factor-stimulated chondrocytes to authentic, exogenous .N = O led to an increase of PGE2 synthesis from 5.6 +/- 1.7 of untreated cells to 15.8 +/- 6.8 ng/10(6) of .N = O treated cells within the 1st h. This was followed by a suppression of PGE2 synthesis within the next 2 h.