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

Placenta. 2006 Jun-Jul;27(6-7):576-86. doi: 10.1016/j.placenta.2005.07.005. Epub 2005 Sep 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Line, Tumor
  • Cells, Cultured
  • Choriocarcinoma / drug therapy
  • Choriocarcinoma / metabolism
  • Choriocarcinoma / pathology
  • Chorion / drug effects
  • Chorion / metabolism
  • Chorion / pathology
  • Cyclooxygenase 2 / biosynthesis*
  • Cyclooxygenase 2 / genetics
  • Dinoprostone / biosynthesis*
  • Dinoprostone / genetics
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Humans
  • Interleukin-1 / pharmacology*
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / metabolism*
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Pregnancy
  • Prostaglandin-E Synthases
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trophoblasts / drug effects*
  • Trophoblasts / metabolism
  • Trophoblasts / pathology
  • Up-Regulation / drug effects

Substances

  • Interleukin-1
  • Membrane Proteins
  • RNA, Messenger
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Intramolecular Oxidoreductases
  • PTGES protein, human
  • Prostaglandin-E Synthases
  • Dinoprostone