The differential regulation of group II(A) and group V low molecular weight phospholipases A2 in cultured rat astrocytes

Abstract

In astrocytes, cytokines stimulate the release of secretory phospholipase A2 (sPLA2) activity and group II(A) sPLA2 expression. This paper reports that two sPLA2 isoforms, group II(A) and group V, are in fact expressed by astrocytes. Our studies showed that tumor necrosis factor α (TNFα) enhanced the mRNA of both isoforms, but the time courses of enhancement differed; group V was induced much faster than group II(A). Moreover, TNFα stimulated both the NF-κB 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 TNFα, and NF-κB 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 TNFα and that blocking phosphatidylinositol 3-kinase activity fully reversed the effect of TNFα. Furthermore, in astrocytes, TNFα-induced release of sPLA2 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 II(A) and group V sPLA2 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 II(A), 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 sPLA2 expression in a manner suggesting the existence of regulation of post-transcriptional events.