Suppression of inducible cyclooxygenase 2 gene transcription by aspirin and sodium salicylate
Suppression of inducible cyclooxygenase 2 gene transcription by aspirin and sodium salicylate
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DOI：
10.1073/pnas.96.9.5292
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发表时间：
1999-04-27
影响因子：
11.1
通讯作者：
Wu, KK
中科院分区：
文献类型：
--
作者：
Xu, XM;Sansores-Garcia, L;Wu, KK
水杨酸钠的药理作用不能通过抑制环氧化酶（COX）活性来解释，本文研究了阿司匹林和水杨酸钠对人脐静脉内皮细胞和包皮成纤维细胞COX-2表达的影响。治疗浓度的阿司匹林和水杨酸钠均可阻断白细胞介素-lp和12-肉豆蔻酸13-醋酸酯诱导的COX-2 mRNA和蛋白水平。在无胎牛血清培养24 h的细胞中，抑制作用更为明显，提示其可能与细胞周期有关。水杨酸抑制新生COX-2转录物的合成，但对COX-2 mRNA的稳定性没有影响，它以浓度依赖的方式抑制COX-2启动子的活性。在阿司匹林预处理（10和30 mg/kg）的小鼠中，脂多糖刺激后，腹腔巨噬细胞中COX-2 mRNA的表达被明显抑制，这些发现表明水杨酸部分通过抑制COX-2的诱导来发挥其抗炎作用。从而减少促炎前列腺素的合成。
The pharmacological action of salicylate cannot be explained by its inhibition of cyclooxygenase (COX) activity, In this report, the effects of aspirin and sodium salicylate on COX-2 expressions in human umbilical vein endothelial cells and foreskin fibroblasts were evaluated. Aspirin and sodium salicylate at therapeutic concentrations equipotently blocked COX-2 mRNA and protein levels induced by interleukin-lp and phorbol 12-myristate 13-acetate. The suppressing effect was more pronounced in cultured cells deprived of fetal bovine serum for 24 h, suggesting that it may be cell cycle related. Salicylate inhibited nascent COX-2 transcript synthesis but had no effect on COX-2 mRNA stability, It inhibited COX-2 promoter activity in a concentration-dependent manner, In mice pretreated with aspirin (10 and 30 mg/kg), followed by challenge with lipopolysaccharide, COX-2 mRNA expression in peritoneal macrophages was markedly suppressed, These findings suggest that salicylate exerts its antiinflammatory action in part by suppressing COX-2 induction, thereby reducing the synthesis of proinflammatory prostaglandins.