Multiple second messenger pathways regulate IL-1 beta-induced expression of PGHS-2 mRNA in normal human skin fibroblasts.
Very little is known about the specific regulation of PGHS-2 mRNA compared with PGHS-1 mRNA. Using normal human fibroblasts, we show that at baseline there is constitutive expression of PGHS-1 mRNA and barely detectable amounts of PGHS-2 mRNA. There was a marked increase in PGHS-2 mRNA transcription following exposure to IL-1 beta. Maximal expression of PGHS-2 mRNA occurred with concentrations of IL-1 beta > or = 1 ng/ml at 3 hours after stimulation. Downregulation of protein kinase C (PKC) activity by pretreating fibroblast cultures with PMA inhibited IL-1-induced PGHS-2 mRNA expression without affecting the constitutive expression of PGHS-1 mRNA. The addition of various PKC inhibitors also blocked the IL-1 beta induction of PGHS-2 mRNA but did not alter PGHS-1 mRNA expression; inhibitors of protein kinase A (PKA) or tyrosine kinase (TK) had only a limited effect on IL-1 beta-induced PGHS-2 mRNA expression. These findings show that IL-1 beta increases PGHS-2 mRNA, at least in part, via activation of PKC. Activation of PKA or TK appears to have a more limited role in this process.
Warnock
L J
LJ
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Hunninghake
G W
GW
D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000145:classification / Q000235:genetics*; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger / Q000378:metabolism*; D012016:Reference Values; D015290:Second Messenger Systems / Q000502:physiology*; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007375:Interleukin-1; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D011451:Prostaglandin-Endoperoxide Synthases; D013755:Tetradecanoylphorbol Acetate