Js. Won et al., Forskolin inhibits expression of inducible nitric oxide synthase mRNA via inhibiting the mitogen activated protein kinase in C6 cells, MOL BRAIN R, 89(1-2), 2001, pp. 1-10
This study has demonstrated the mechanism of protein kinase A (PKA)-depende
nt inhibition of astrocytic nitric oxide production and inducible NO syntha
se mRNA expression induced by lipopolysaccharide. In C6 glioma cells, the s
timulation with lipopolysaccharide (LPS; 1 mug/ml) evoked increases of nitr
ic oxide (NO) production, NO synthase (iNOS) mRNA expression, phosphorylati
on of p38 mitogen activated protein kinase (p-p38), and the activation of N
F kappaB. LPS-induced NO production and iNOS mRNA expression were inhibited
by the pretreatment with forskolin (FSK; 5 muM) in a dose-dependent manner
, and which were reversed by PKA inhibition by compound H89. Furthermore, L
PS-induced increases of p-p38, but not activation of NF kappaB, were also r
educed by FSK and H89 reversed the FSK-induced inhibition response. The dos
e-dependent inhibition of NO production and iNOS mRNA expression by compoun
d SB203580 (p38 inhibitor) suggests the participation of p38 in PKA-depende
nt inhibition of LPS-induced NO production and iNOS mRNA expression. Howeve
r. the activation of NF kappaB by LPS also not affected by SB203580. Theref
ore, our results suggest that, in C6 glioma cells, LPS-induced NO productio
n acid iNOS gene expression may be regulated by PKA pathway through the red
uction of activity of p38 kinase. This inhibitory role of PRA may not invol
ve the activation of NF kappaB. (C) 2001 Elsevier Science B.V. All rights r
eserved.