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

Abstract Cytokines have been implicated in pancreatic β-cell destruction leading to type 1 diabetes. Exposure to interleukin-1β (IL-1β) of pancreatic β-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 β-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-1β stimulated the formation of NO and PGE2 by pancreatic β-cells. L-NMMA completely inhibited IL-1β-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-1β-induced promoter activity, gene transcription and protein expression of COX-2 in pancreatic β-cells. Therefore, we concluded that NO-affected COX-2 activity is directly linked to COX-2 gene transcription and protein expression in pancreatic β-cells. The identification of a novel interaction of NO on the COX signaling pathway in β-cells provides a strategy of intervention for further evaluating the role of NO and PGE2 in autoimmune diabetes.

Edited by Chong-Rong SUN