Extracellular nucleotides induce COX-2 up-regulation and prostaglandin E2 production in human A549 alveolar type II epithelial cells.
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.
Marcet
Brice
B
Institute of Interdisciplinary Research, IRIBHM, Université Libre de Bruxelles, and Department of Medical Chemistry, Erasme Hospital, Brussels, Belgium. marcet@ipmc.cnrs.fr
Libert
Frédérick
F
Boeynaems
Jean-Marie
JM
Communi
Didier
D
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
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