title: Central role for protein kinase C in oxytocin and epidermal growth factor stimulated cyclooxygenase 2 expression in human myometrial cells.
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.
authors.forename: Elien
authors.initials: E
authors.lastname: Wouters
authors.forename: Claire A
authors.initials: CA
authors.lastname: Hudson
authors.forename: Craig A
authors.initials: CA
authors.lastname: McArdle
authors.affiliation: University of Bristol, School of Clinical Sciences (Obstetrics and Gynaecology), Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK. a.lopezbernal@bristol.ac.uk.
authors.forename: Andrés López
authors.initials: AL
authors.lastname: Bernal
mesh_terms: D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D009215:Myometrium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D010121:Oxytocin / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D010121:Oxytocin; D004815:Epidermal Growth Factor; D051546:Cyclooxygenase 2; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D013755:Tetradecanoylphorbol Acetate