Regulation of c-fos and c-jun gene expression by lipopolysaccharide and cytokines in primary cultured astrocytes: effect of PKA and PKC pathways.

Abstract

The effects of lipopolysaccharide (LPS) and several cytokines on the c-fos and c-jun mRNA expression were examined in primary cultured astrocytes. Either LPS (500 ng/mL) or interferon-gamma (IFN-gamma; 5 ng/mL) alone increased the level of c-fos mRNA (1 h). However, tumor necrosis factor-alpha (TNF-alpha; 10 ng/mL) or interleukin-1beta (IL-1beta; 5 ng/mL) alone showed no significant induction of the level of c-fos mRNA. TNF-alpha showed a potentiating effect in the regulation of LPS-induced c-fos mRNA expression, whereas LPS showed an inhibitory action against IFN-gamma-induced c-fos mRNA expression. LPS, but not TNF-alpha, IL-1beta and IFN-gamma, increased the level of c-jun mRNA (1 h). TNF-alpha and IFN-gamma showed an inhibitory action against LPS-induced c-jun mRNA expression. Both phorbol 12-myristate 13-acetate (PMA; 2.5 mM) and forskolin (FSK; 5 mM) increased the c-fos and c-jun mRNA expressions. In addition, the level of c-fos mRNA was expressed in an antagonistic manner when LPS was combined with PMA. When LPS was co-treated with either PMA or FSK, it showed an additive interaction for the induction of c-jun mRNA expression. Our results suggest that LPS and cytokines may be actively involved in the regulation of c-fos and c-jun mRNA expressions in primary cultured astrocytes. Moreover, both the PKA and PKC pathways may regulate the LPS-induced c-fos and c-jun mRNA expressions in different ways.