The differential regulation of group IIA and group V low molecular weight phospholipases A2 in cultured rat astrocytes

In astrocytes, cytokines stimulate the release of secretory phospholipase A(2) (sPLA(2)) activity and group IIA sPLA(2), expression. This paper reports that two sPLA(2) isoforms, group IIA and group V, are in fact expressed by astrocytes, Our studies showed that tumor necrosis factor alpha (TNF alpha) enhanced the mRNA of both isoforms, but the time courses of enhancement differed; group V was induced much faster than group IIA. Moreover, TNF alpha stimulated both the NF-kappa B and mitogen-activated protein (MAP) kinase (extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 MAP kinase) signaling pathways in astrocytes, Interestingly, PI 3-kinase activity also was enhanced by TNF alpha, and NF-kappa B pathway was involved in mediating its effect. Specific inhibitors were used to show that both extracellular signal-regulated kinase and p38 MAP kinase may contribute to the effect of TNF alpha and that blocking phosphatidylinositol 3-kinase activity fully reversed the effect of TNF alpha. Furthermore, in astrocytes, TNF alpha-induced release of sPLA(2) activity was partially reversed by thyroid hormone and almost abolished by growth factors. This phenomenon was accompanied by a less marked increase in both group IIA and group V sPLA(2) mRNA. In the presence of growth factors, the increase in group V mRNA was inhibited early and transiently, in contrast to what was observed with group IIA, which was more persistently inhibited. Although a transcriptional effect of thyroid hormone or growth factors in astrocytes cannot be definitively excluded, both types of factor interfered with sPLA(2) expression in a manner suggesting the existence of regulation of post-transcriptional events.