Abstract

Cyclooxygenase-2 (COX-2) expression isassociated with many aspects of physiological and pathological conditions,including pancreatic β -cell dysfunction. Prostaglandin E2 (PGE2) production,as a consequence of COX-2 gene induction, has been reported to impair β -cellfunction. The molecular mechanisms involved in the regulation of COX-2 geneexpression are not fully understood. We previously demonstrated thattranscription factor Elk-1 significantly upregulated COX-2 gene promoteractivity. In this report, we used pancreatic β -cell line (INS-1) to explorethe relationships between Elk-1 and COX-2. We first investigated the effects ofElk-1 on COX-2 transcriptional regulation and expression in INS-1 cells. Wethus undertook to study the binding of Elk-1 to its putative binding sites inthe COX-2 promoter. We also analysed glucose-stimulated insulin secretion(GSIS) in INS-1 cells that overexpressed Elk-1. Our results demonstrate thatElk-1 efficiently upregulates COX-2 expression at least partly through directlybinding to the -82/-69 region of COX-2 promoter. Overexpression of Elk-1inhibits GSIS in INS-1 cells. These findings will be helpful for betterunderstanding the transcriptional regulation of COX-2 in pancreatic β -cell.Moreover, Elk-1, the transcriptional regulator of COX-2 expression, will be apotential target for the prevention of β -cell dysfunction mediated by PGE2.