The gene encoding cyclooxygenase-2 is regulated by IL-1β and prostaglandins in 832/13 rat insulinoma cells

The pro-inflammatory cytokine IL-1β leads to losses in functional β-cell mass in part by inducing the expression of genes that produce soluble mediators of inflammation, such as cyclooxygenase-2 (COX2). In the current study, we sought to understand what factors control the COX2 gene in response to IL-1β and how prostaglandins downstream of COX2 impact pro-inflammatory gene transcription in pancreatic β-cells. We analyzed COX2 gene expression in response to different maneuvers impacting NF-κB proteins. Also, we report alterations in the expression of COX2, EP-3 and EP-4 receptor genes by PGD2 and PGE2. Moreover, we examined whether PGD2 and PGE2 regulated NF-κB and interferon-gamma activated sequence (GAS) reporter gene activity. IL-1β-mediated induction of the COX2 gene requires the p65 and p50 subunits of NF-κB. In addition, PGD2 and PGE2 coordinately alter COX2 and EP receptor gene expression patterns and potentiate the cytokine-mediated transcriptional activity of promoters containing NF-κB or GAS response elements.