CDC对胰岛β细胞中COX-2表达及PGE2生成的影响

Inhibitory Effects of 12/15 LOX Inhibitor CDC on COX-2 Gene Expression and PGE2 Generation in Pancreatic β-cells

目的观察12/15脂氧合酶抑制剂CDC对大鼠胰岛β细胞中环加氧酶2(COX-2)的表达及前列腺素E2(PGE2)生成的影响,并初步探讨其机制。方法体外培养大鼠胰岛β细胞系INS-1细胞,加入细胞因子IL-1β诱导COX-2蛋白的表达,然后采用Western印迹的方法观察12/15脂氧合酶抑制剂cin-naminyl-3,4-dihydroxy-α-cyanocinnamate(CDC)对COX-2蛋白表达的影响;借助萤光素酶报告基因技术检测CDC对COX-2启动子转录活性的影响,最后用放射免疫法了解CDC对胰岛β细胞中PGE2生成的抑制作用。结果细胞因子IL-1β能够在大鼠胰岛β细胞系INS-1中诱导COX-2基因的表达,而12/15脂氧合酶抑制剂CDC能够呈剂量依赖抑制IL-1β所诱导的COX-2蛋白的表达。结论12/15脂氧合酶抑制剂能够明显抑制炎性因子IL-1β所诱导的胰岛β细胞中COX-2的表达和炎性介质PGE2的生成。

Objective To investigate the mechanism of inhibitory effects of CDC on cox-2 gene expression and PGE2 generation in rat pancreatic β- cells. Method The inhibitory effects of CDC on COX-2 expression were determined by Western blot analysis. Pancreaticβ-cell line INS-1 cells transfected with pGL3-cox-2-promoter were assayed for luciferase activity and PGE2 production in INS-1 cells was measured by RIA. Results IL-l-induced COX-2 protein expression was decreased by 12/15 LOX inhibitor CDC in a dose-dependent manner. Conclusion The 12/15 LOX inhibitor CDC may inhibit IL-1β-induced PGE2 production in pancreatic β-cells by inhibiting both 12/15 LOX and cox-2 enzyme.