Inflammatory factors stimulate expression of group II phospholipase A₂ in rat cultured astrocytes: Two distinct pathways of the gene expression

Inflammatory factors such as tumor necrosis factor (TNF), interleukin 1 (IL-1), and lipopolysaccharide (LPS) greatly enhance the expression of group II phospholipase A₂ (PLA₂-II) mRNA, leading to increased secretion of PLA₂-II enzyme from rat-cultured astrocytes. The potent antiinflammatory agent dexamethasome suppressed the PLA₂-II expression induced by LPS. In vivo studies also demonstrated that the level of PLA₂-II mRNA in the brain increased with intravenous injection of LPS. These results suggest that PLA₂-II in the brain plays important roles in the inflammatory response. Agents which increase intracellular cAMP concentration did not stimulate PLA₂-II expression by themselves but selectively enhanced TNF-induced PLA₂-II expression about 5-fold. Phorbol ester, a well known protein kinase C activator, increased the PLA₂-II expression. H-7, a protein kinase C inhibitor, inhibited the LPS-induced PLA₂-H expression, but did not inhibit the TNF-induced one. Therefore, we conclude that the TNF-activated pathway differs from the LPS-activated one: the former is enhanced by cAMP and the latter involves protein kinase C.