Regulation of c-Fos and c-Jun Gene Expression by Lipopolysaccharide and Cytokines in Primary Cultured Astrocytes: Effect of PKA and PKC Pathways

  • Suh Hong-Won (Department of Pharmacology College of Medicine and Institute of Natural Medicine, Hallym University) ;
  • Choi Seong-Soo (Department of Pharmacology College of Medicine and Institute of Natural Medicine, Hallym University) ;
  • Lee Jin-Koo (Department of Pharmacology College of Medicine and Institute of Natural Medicine, Hallym University) ;
  • Lee Han-Kyu (Department of Pharmacology College of Medicine and Institute of Natural Medicine, Hallym University) ;
  • Han Eun-Jung (Department of Pharmacology College of Medicine and Institute of Natural Medicine, Hallym University) ;
  • Lee Jongho (Department of Pharmacology College of Medicine and Institute of Natural Medicine, Hallym University)
  • Published : 2004.04.01

Abstract

The effects of lipopolysaccharide (LPS) and several cytokines or the c-fos and c-jun mRNA expression were examined in primary cultured astrocytes. Either LPS (500 ng/mL) or inter-feron-$\gamma$ (IFN-$\gamma$ 5 ng/mL) alone increased the level of c-fos mRNA (1 h). However, tumor necro-sis factor-$\alpha$ (TNF-$\alpha$; 10 ng/mL) or interleukin-4 (IL-1$\beta$: 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-Y-induced c-fos mRNA expression. LPS, but not TNF-$\alpha$, IL-1$\beta$ 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.

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