N-acetyl cysteine inhibits induction of NO production by endotoxin or cytokine stimulated rat peritoneal macrophages, C-6 glial cells and astrocytes
N-acetyl cysteine inhibits induction of NO production by endotoxin or cytokine stimulated rat peritoneal macrophages, C-6 glial cells and astrocytes
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DOI：
10.1016/s0891-5849(97)00137-8
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发表时间：
1998-01-01
影响因子：
7.4
通讯作者：
Singh, I
中科院分区：
文献类型：
--
作者：
Pahan, K;Sheikh, FG;Singh, I
本研究强调了n -乙酰半胱氨酸（NAC）在抑制脂多糖（LPS）和细胞因子诱导腹膜巨噬细胞、C-6胶质细胞和原代星形胶质细胞NO生成中的重要性。NAC是一种有效的抗氧化剂。LPS、白细胞介素-1 β (IL-1 β)、干扰素- γ (ifn - γ)和肿瘤坏死因子- α (TNF-)单独或联合作用均不同程度诱导NO的产生。在这些刺激的2小时前加入NAC，可能会阻止巨噬细胞、星形胶质细胞和C-6胶质细胞中NO生成的增加。NAC诱导NO生成的减少伴随着诱导型一氧化氮合酶（iNOS）活性的降低，iNOS抗体免疫印迹检测的iNOS蛋白活性降低，逆转录酶偶联聚合酶链反应（RT-PCR）检测的iNOS mRNA活性降低。时间过程研究表明，NAC在LPS前2 h加入时抑制作用最大，在LPS后加入NAC，抑制程度随着时间间隔的增加而逐渐降低。除NAC外，另一种抗氧化剂吡咯烷二硫代氨基甲酸酯（PDTC）也能有效抑制NO的生成。由于NF-kappa B的激活是诱导iNOS的必要条件，我们检测了NAC对hTF-kappa B激活的影响，NAC抑制lps诱导的大鼠腹膜巨噬细胞NF-kappa B的激活表明NAC对诱导iNOS的抑制作用是由于抑制NF-kappa B。除了NO， NAC还阻断了内毒素激活的大鼠腹膜巨噬细胞tnf - α的产生。这些结果提示巨噬细胞中iNOS和tnf - α的表达确实与氧自由基有关。讨论了这些结果在控制活化的巨噬细胞和胶质细胞释放的细胞因子的各种有害影响方面的重要性。(C) 1997爱思唯尔科学有限公司
The present study underscores the importance of N-acetyl cysteine (NAC), a potent antioxidant, in inhibiting the induction of NO production by lipopolysaccharides (LPS) and cytokines in peritoneal macrophages, C-6 glial cells and primary astrocytes. LPS, interleukin-1 beta (IL-1 beta), interferon-gama (IFN-gamma) and tumor necrosis factor-alpha (TNF-) alone or in combinations induced the production of NO to different degrees. NAC when added 2 h earlier to the addition of these stimuli potentially blocked the increase in NO production in macrophages, astrocytes and C-6 glial cells. The decrease in NO production by NAC was accompanied by a decrease in inducible nitric oxide synthase (iNOS) activity, in iNOS protein detected by immunoblot analysis with antibodies against iNOS, and in iNOS mRNA determined by reverse transcriptase coupled polymerase chain reaction (RT-PCR). Time course studies show that inhibition was maximum when NAC was added 2 h prior to the addition of LPS and the degree of inhibition decreased progressively with the increase in time interval when NAC was added after the addition of LPS. In addition to NAC, another antioxidant pyrrolidine dithiocarbamate (PDTC) was also found to inhibit the induction of NO production effectively. Since activation of NF-kappa B is necessary for the induction of iNOS, we examined the effect of NAC on the activation of hTF-kappa B. Inhibition of LPS-induced activation of NF-kappa B by NAC in rat peritoneal macrophages suggests that the inhibitory effect of NAC on the induction of iNOS is due to the inhibition of NF-kappa B. Besides NO, NAC also blocked the production of TNF-alpha in rat peritoneal macrophages activated with endotoxin. These results suggest that expression of iNOS and TNF-alpha in macrophages do involve oxygen radicals. The importance of these results in relation to controlling various harmful effects of cytokines released by activated macrophages and glial cells is discussed. (C) 1997 Elsevier Science Inc.