Potential Role of NO in Modulation of COX-2 Expression and PGE2 Production in Pancreatic β-cells  

作　　者：Jia-JianLING Yu-JieSUN Dong-YaZHU QiCHEN XiaoHAN 

机构地区：[1]TheKeyLaboratoryofHumanFunctionalGenomicsofJiangsuProvince,NanjingMedicalUniversity,Nanjing210029,China [2]SchoolofPharmacy.NanjingMedicalUniversity,Nanjing210029,China

出　　处：《Acta Biochimica et Biophysica Sinica》2005年第2期139-146,共8页生物化学与生物物理学报（英文版）

基　　金：This work was supported by a grant from the National Natural Science Foundation of China(No.30370676)

摘　　要：Cytokines have been implicated in pancreatic P-cell destruction leading to type I diabetes. Exposure to interleuken-1beta (IL-1beta) of pancreatic beta-cells induces expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequent formation of nitric oxide (NO) and prostaglandin E2 (PGE2) may impair beta-cell function. Using NOS inhibitor N-G-monomethyl-L-arginine (L-NMMA), we have further investigated the relation between NO formation and COX-2 expression. IL-1beta stimulated the formation of NO and PGE2 by pancreatic beta-cells. L-NMMA completely inhibited IL-1beta-induced NO formation and attenuated PGE2 production. COX-2 gene transcription level and protein expression were determined by real-time PCR, Western blot and luciferase analysis. L-NMMA inhibited IL-1beta-induced promoter activity, gene transcription and protein expression of COX-2 in pancreatic beta-cells. Therefore, we concluded that NO-affected COX-2 activity is directly linked to COX-2 gene transcription and protein expression in pancreatic beta-cells. The identification of a novel interaction of NO on the COX signaling pathway in beta-cells provides a strategy of intervention for further evaluating the role of NO and PGE2 in autoimmune diabetes.Cytokines have been implicated in pancreatic P-cell destruction leading to type I diabetes. Exposure to interleuken-1beta (IL-1beta) of pancreatic beta-cells induces expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequent formation of nitric oxide (NO) and prostaglandin E2 (PGE2) may impair beta-cell function. Using NOS inhibitor N-G-monomethyl-L-arginine (L-NMMA), we have further investigated the relation between NO formation and COX-2 expression. IL-1beta stimulated the formation of NO and PGE2 by pancreatic beta-cells. L-NMMA completely inhibited IL-1beta-induced NO formation and attenuated PGE2 production. COX-2 gene transcription level and protein expression were determined by real-time PCR, Western blot and luciferase analysis. L-NMMA inhibited IL-1beta-induced promoter activity, gene transcription and protein expression of COX-2 in pancreatic beta-cells. Therefore, we concluded that NO-affected COX-2 activity is directly linked to COX-2 gene transcription and protein expression in pancreatic beta-cells. The identification of a novel interaction of NO on the COX signaling pathway in beta-cells provides a strategy of intervention for further evaluating the role of NO and PGE2 in autoimmune diabetes.

关 键 词：OXIDE CYCLOOXYGENASE-2 pancreatic beta-cell prostaglandin E2 

分 类 号：R587.1[医药卫生—内分泌] R392.1[医药卫生—内科学]