Prostaglandin F2-alpha receptor regulation in human uterine myocytes

Investigations of the modulation of prostaglandin F_2α receptor (FP) expression in primary cultures of human uterine myocytes showed that FP mRNA expression was reduced by progesterone, unaltered by cAMP (8-bromo cAMP or forskolin), but increased by the PKA antagonist H89. Interleukin (IL)-1β, tumour necrosis factor-alpha and oxytocin increased FP mRNA expression and IL-6 and prostaglandin E₂ reduced FP mRNA expression. The changes in FP protein levels were similar to the mRNA responses. We found that the IL-1β-induced increase in FP expression was mediated at least in part via protein kinase C (PKC), but was independent of mitogen-activated protein kinase, phospholipase C and PI3 kinase. Since IL-1β activates NFκB, AP-1 and C/EBP, we over-expressed these transcription factors alone and in combination and found that only NFκB alone increased FP mRNA expression. Finally, we found that the IL-1β-induced increase in FP expression was unaffected by progesterone and/or cAMP, but was accentuated by H89. These data suggest that the pregnancy-induced down-regulation in myometrial FP expression is mediated by progesterone and cAMP and that the increase with labour is induced by inflammatory cytokine activation of PKC and NFκB.