Involvement of p38 mitogen-activated protein kinase in lipopolysaccharide-induced iNOS and COX-2 expression in J774 macrophages
Involvement of p38 mitogen-activated protein kinase in lipopolysaccharide-induced iNOS and COX-2 expression in J774 macrophages
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DOI：
10.1046/j.1365-2567.1999.00747.x
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发表时间：
1999-05-01
期刊：
影响因子：
6.4
通讯作者：
Lin, WW
中科院分区：
文献类型：
--
作者：
Chen, BC;Chen, YH;Lin, WW
脂多糖引起的J774巨噬细胞亚硝酸盐和前列腺素E-2(PGE(2))的释放均被p38丝裂原活化蛋白激酶(MAPK)特异性抑制剂SE 203580以浓度依赖的方式抑制。对亚硝酸盐和前列腺素E_2反应的半数抑制浓度(IC_(50))分别为1u M和0.5u M。SE 203580和脂多糖同时作用后，抑制作用显著，而在脂多糖处理后6小时加入SE 203580，抑制作用明显减弱。同时，SB 203580可降低脂多糖诱导的诱导型一氧化氮合酶(INOS)和环氧合酶-2(COX-2)蛋白及其稳态表达水平。SB 203580对核因子-kappaB、激活蛋白-1和p38MAPK的激活也有抑制作用。这些结果提示，p38MAPK在内毒素诱导的iNOS和COX-2蛋白表达的转录水平调节中起重要作用。
Both the nitrite and prostaglandin E-2 (PGE(2)) release caused by lipopolysaccharide (LPS) in J774 macrophages are inhibited by SE 203580, a specific p38 mitogen-activated protein kinase (MAPK) inhibitor, in a concentration-dependent manner. The 50% inhibitory concentration (IC50) for nitrite and PGE(2) responses was 1 mu M and 0.5 mu M, respectively. Inhibition was marked following simultaneous treatment with SE 203580 and LPS, and was much reduced when SE 203580 was added 6 hr after LPS treatment. In parallel, LPS induction of inducible NO synthase (iNOS) and cyclo-oxygenase-2 (COX-2) proteins and their steady-state levels of mRNA were reduced by SB 203580. LPS activation of nuclear factor-kappa B (NF-kappa B), activator protein-1 (AP-1) and p38 MAPK was also inhibited by SB 203580. These results suggest a crucial role of p38 MAPK in regulation of the transcriptional level of endotoxin LPS-induced iNOS and COX-2 protein expression.