Xu X M, Sansores-Garcia L, Chen X M, Matijevic-Aleksic N, Du M, Wu K K
Vascular Biology Research Center and Division of Hematology, University of Texas-Houston Medical School, Houston, TX 77030, USA.
Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5292-7. doi: 10.1073/pnas.96.9.5292.
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-1beta 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.
水杨酸盐的药理作用无法通过其对环氧合酶（COX）活性的抑制来解释。在本报告中，评估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中COX - 2表达的影响。治疗浓度的阿司匹林和水杨酸钠等效地阻断了由白细胞介素 - 1β和佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯诱导的COX - 2 mRNA和蛋白质水平。在剥夺胎牛血清24小时的培养细胞中，抑制作用更为明显，表明其可能与细胞周期相关。水杨酸盐抑制新生COX - 2转录本的合成，但对COX - 2 mRNA稳定性没有影响。它以浓度依赖的方式抑制COX - 2启动子活性。在用阿司匹林（10和30 mg/kg）预处理的小鼠中，随后用脂多糖攻击，腹膜巨噬细胞中COX - 2 mRNA表达明显受到抑制。这些发现表明，水杨酸盐部分通过抑制COX - 2的诱导发挥其抗炎作用，从而减少促炎前列腺素的合成。
