Lj. Warnock et Gw. Hunninghake, MULTIPLE SECOND MESSENGER PATHWAYS REGULATE IL-1-BETA-INDUCED EXPRESSION OF PGHS-2 MESSENGER-RNA IN NORMAL HUMAN SKIN FIBROBLASTS, Journal of cellular physiology, 163(1), 1995, pp. 172-178
Very little is known about the specific regulation of PGHS-2 mRNA comp
ared with PGHS-1 mRNA. Using normal human fibroblasts, we show that at
baseline there is constitutive expression of PGHS-1 mRNA and barely d
etectable amounts of PGHS-2 mRNA. There was a marked increase in PGHS-
2 mRNA transcription following exposure to IL-1 beta. Maximal expressi
on of PCHS-2 mRNA occurred with concentrations of IL-1 beta greater th
an or equal to 1 ng/ml at 3 hours after stimulation. Downregulation of
protein kinase C (PKC) activity by pretreating fibroblast cultures wi
th PMA inhibited IL-1-induced PGHS-2 mRNA expression without affecting
the constitutive expression of PGHS-1 mRNA. The addition of various P
KC inhibitors also blocked the IL-1 beta induction of PCHS-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-in
duced PCHS-2 mRNA expression. These findings show that IL-1 beta incre
ases 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. (C)
1995 Wiley-Liss, Inc.