http://www.abbs.info E-mail: [email protected]
ISSN
1672-9145
Acta Biochim Biophys Sin
2005, 37(2): 139–146
CN 31-1940/Q
Potential Role of NO in Modulation of COX-2 Expression and PGE2 Production
in Pancreatic b-cells
Jia-Jian LING, Yu-Jie SUN, Dong-Ya ZHU1, Qi CHEN, and Xiao HAN*
The Key Laboratory
of Human Functional Genomics of Jiangsu Province, Nanjing Medical University,
Nanjing 210029, China;
1School of Pharmacy, Nanjing Medical
University, Nanjing 210029, China
Abstract Cytokines have been implicated in pancreatic b-cell destruction leading to type 1 diabetes. Exposure to interleukin-1b (IL-1b) of pancreatic b-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 b-cell function. Using NOS inhibitor NG-monomethyl-L-arginine (L-NMMA), we have further investigated the relation between NO formation and COX-2 expression. IL-1b stimulated the formation of NO and PGE2 by pancreatic b-cells. L-NMMA completely inhibited IL-1b-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-1b-induced promoter activity, gene transcription and protein expression of COX-2 in pancreatic b-cells. Therefore, we concluded that NO-affected COX-2 activity is directly linked to COX-2 gene transcription and protein expression in pancreatic b-cells. The identification of a novel interaction of NO on the COX signaling pathway in b-cells provides a strategy of intervention for further evaluating the role of NO and PGE2 in autoimmune diabetes.
Key words nitric oxide; cyclooxygenase-2 ; pancreatic b-cell; prostaglandin E2
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Received: October 27, 2004 Accepted: January 7, 2005
This work was supported by a grant from the National Natural Science Foundation of China (No. 30370676)
*Corresponding author: Tel, 86-25-86862731/86862733; E-mail, [email protected]