Multiple second messenger pathways regulate IL‐β‐induced expression of PGHS‐2 mRNA in normal human skin fibroblasts

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Abstract
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‐β. Maximal expression of PGHS‐2 mRNA occurred with concentrations of IL‐β ≥ 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‐β 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‐β‐induced PGHS‐2 mRNA expression. These findings show that IL‐β 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.