title: Extracellular nucleotides induce COX-2 up-regulation and prostaglandin E2 production in human A549 alveolar type II epithelial cells.
abstract: Extracellular nucleotides regulate ion transport, mucociliary clearance as well as inflammatory properties of the airway epithelium by acting on P2 receptors. Cyclooxygenase-2 (COX-2) is a key enzyme involved in the synthesis of prostaglandins during inflammation. In this study, using calcium imaging, DNA microarray experiments, real-time Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and prostaglandin E2 (PGE2) measurement, we show for the first time that ATP, UTP or INS365 compound (P2Y2 receptor agonists) up-regulate COX-2 expression by approximately 3-fold and enhance the release of PGE2 in human A549 airway epithelial cells. Our data suggest that P2Y receptors may represent putative targets in airway inflammatory diseases.
authors.affiliation: Institute of Interdisciplinary Research, IRIBHM, Université Libre de Bruxelles, and Department of Medical Chemistry, Erasme Hospital, Brussels, Belgium. marcet@ipmc.cnrs.fr
authors.forename: Brice
authors.initials: B
authors.lastname: Marcet
authors.forename: Frédérick
authors.initials: F
authors.lastname: Libert
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Boeynaems
authors.forename: Didier
authors.initials: D
authors.lastname: Communi
mesh_terms: D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D009711:Nucleotides / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology; D058910:Purinergic P2 Receptor Agonists; D012333:RNA, Messenger / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000235:genetics; D058473:Receptors, Purinergic P2Y2; D015854:Up-Regulation
chemical_list: D007295:Inositol Phosphates; D009711:Nucleotides; C546385:P2RY2 protein, human; D058910:Purinergic P2 Receptor Agonists; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; C099845:purinoceptor P2Y6; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D002118:Calcium