Central role for protein kinase C in oxytocin and epidermal growth factor stimulated cyclooxygenase 2 expression in human myometrial cells

Elien Wouters, Claire A. Hudson, Craig A. McArdle, Andrés López Bernal

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background: Prostaglandins are important mediators of uterine contractility and cervical ripening during labour. Cyclooxygenase-2 (COX-2), also known as prostaglandin-endoperoxide synthase 2, is a rate limiting enzyme involved in the conversion of arachidonic acid into prostaglandins at parturition. In this paper, the pathways underlying agonist-induced cyclooxygenase-2 expression in human myometrial cells were studied. Results: Myometrial cells were stimulated with different agonists: oxytocin (OXT), epidermal growth factor (EGF), interleukin-1β (IL1β), and phorbol-12-myristate-13-acetate (PMA) alone and in the presence of specific signalling pathway inhibitors. The nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB) pathway was inhibited by means of the IKK-2 inhibitor TPCA-1. Signalling through extracellular signal-regulated kinases (ERK) was inhibited using the MEK1/2 inhibitor PD-184352. Bisindolylmaleimide-I was used to inhibit protein kinase C (PKC) signalling. COX-2 expression and ERK phosphorylation were measured using immunoblotting.OXT induced COX-2 expression by activating PKC and ERK. EGF increased COX-2 expression via stimulation of PKC, ERK and NFKB. As expected, the pro-inflammatory cytokine IL1β induced COX-2 expression by activating PKC- and NFKB-dependent pathways. Stimulation of PKC directly with PMA provoked strong COX-2 expression. Conclusions: PKC plays a central role in OXT and EGF induced COX-2 expression in human myometrial cells. However, other pathways, notably ERK and NFKB are also involved to an extent which depends on the type of agonist used.

Original languageEnglish
Article number357
JournalBMC Research Notes
Volume7
Issue number1
DOIs
StatePublished - 10 Jun 2014
Externally publishedYes

Keywords

  • Intracellular pathways
  • Parturition
  • Prostaglandin synthase
  • Regulation
  • Uterus

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