title: IL-1beta treatment does not co-ordinately up-regulate mPGES-1 and COX-2 mRNA expression, but results in higher degree of cellular and intracellular co-localization of their immunoreactive proteins in human placenta trophoblast cells.
abstract: PGE2 is involved in initiation and progression of labor in many species. Biosynthesis of PGE2 is mediated by cyclooxygenases (COX) and prostaglandin E synthases (PGES). mPGES-1 and COX-2 form an inducible pathway for PGE2 production in many cell systems. In this study we investigated whether mPGES-1 is involved in cytokine induced PGE2 biosynthesis in human trophoblast cells. We have evaluated the cellular and intracellular co-localization of mPGES-1 and COX-2, as well as cPGES and COX-1 in human trophoblast cells by dual immunofluorescent staining. The effect of IL-1beta on mPGES-1 and COX-2 co-localization, such as would occur with infection, and the regulatory effects of pro-inflammatory cytokines IL-1beta and TNF-alpha on transcriptional activity of mPGES-1 and COX-2 in these cells were also studied. We found that in cultured unstimulated trophoblasts, some cells expressed predominantly either mPGES-1 or COX-2, though there were cells co-expressing both enzymes. With IL-1beta treatment, mPGES-1 and COX-2 became more consistently co-localized. mPGES-1 was not transcriptionally co-induced with COX-2 by the cytokine treatment. We conclude that mPGES-1 is not involved in the inducible COX-2 mediated pathway for PGE2 biosynthesis at the transcriptional level, however, the treatment with IL-1beta results in a higher degree of co-ordination of the mPGES-1 and COX-2 protein immunolocalization, eliciting PGE2 synthesis.
authors.affiliation: CIHR Group in Development and Fetal Health, Department of Physiology and Obstetrics, Gynecology and Medicine, University of Toronto, Toronto, Ontario, Canada M5S1A8. marina.premyslova@utoronto.ca
authors.forename: M
authors.initials: M
authors.lastname: Premyslova
authors.forename: H
authors.initials: H
authors.lastname: Chisaka
authors.forename: K
authors.initials: K
authors.lastname: Okamura
authors.forename: J R G
authors.initials: JR
authors.lastname: Challis
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002822:Choriocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002823:Chorion / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D011247:Pregnancy; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D007375:Interleukin-1; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone