title: The gene encoding cyclooxygenase-2 is regulated by IL-1β and prostaglandins in 832/13 rat insulinoma cells.
abstract: 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 PGD(2) and PGE(2). Moreover, we examined whether PGD(2) and PGE(2) 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, PGD(2) and PGE(2) 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.
authors: Department of Nutrition, University of Tennessee, Knoxville, TN 37996-1920, USA.
authors: Susan J
authors: SJ
authors: Burke
authors: J Jason
authors: JJ
authors: Collier
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics*; D015232:Dinoprostone / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects; D018836:Inflammation Mediators / Q000276:immunology / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000201:enzymology* / Q000276:immunology; D007340:Insulinoma / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology / Q000494:pharmacology*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic; D015230:Prostaglandin D2 / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000235:genetics; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000235:genetics; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D052002:NF-kappa B p50 Subunit; D011453:Prostaglandins; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D015232:Dinoprostone; D015230:Prostaglandin D2