Involvement of the 3'-untranslated region of cyclooxygenase-2 gene in its post-transcriptional regulation through the glucocorticoid receptor.
Functional roles of the 3'-untranslated region (3'-UTR) of the human Cyclooxygenase-2 (COX-2) gene were evaluated by transient transfection using luciferase (Luc) reporter vectors into bovine arterial endothelial cells (BAEC). Insertion of the 3'-UTR into the downstream of a Luc coding region resulted in decreased reporter activity (23%), although insertion into the upstream was no effect. The reporter activity of the downstream insertion but not the upstream insertion was induced by bacterial lipopolysaccharide (LPS). Moreover, LPS selectively stabilized COX-2 mRNA. Next, to evaluate the role of the 3'-UTR together with glucocorticoid receptor (GR), a GR-expression vector was cotransfected with the reporter vector of the downstream insertion of the 3'-UTR. As a result, the LPS-induced reporter activity was suppressed by dexamethasone in a dose-dependent manner. These data suggest that the 3'-UTR of the COX-2 gene is involved in not only the induction by LPS but also the suppression by DEX of COX-2 expression at the post-transcriptional level.
Nishimori
Takeo
T
Department of Pharmacology, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
Inoue
Hiroyasu
H
Hirata
Yukio
Y
D020413:3' Untranslated Regions; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D003907:Dexamethasone / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D014158:Transcription, Genetic
D020413:3' Untranslated Regions; D005938:Glucocorticoids; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases