Regulation of c-fos and c-jun gene expression by lipopolysaccharide and cytokines in primary cultured astrocytes: effect of PKA and PKC pathways.
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.
Suh
Hong-Won
HW
Department of Pharmacology, College of Medicine and Institute of Natural Medicine, Hallym University, 1 Okchun-Dong, Chunchon, Kangwon-Do 200-702, Korea.
Choi
Seong-Soo
SS
Lee
Jin-Koo
JK
Lee
Han-Kyu
HK
Han
Eun-Jung
EJ
Lee
Jongho
J
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000502:physiology; D016762:Genes, fos / Q000187:drug effects / Q000502:physiology*; D016758:Genes, jun / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D011493:Protein Kinase C / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C