Fig. 9

Cultured astrocytes produce inflammatory molecules in a Mek-Erk-dependent manner. A primary astrocyte culture is treated with medium conditioned with lipopolysaccharide (LPS)-stimulated microglia (stimCM) or non-stimulated microglia (non-stimCM). a Various signaling pathways including Erk1/2 are activated by stimCM. b Messenger RNA expression levels for cytokines and chemokines are elevated at 24 h after stimCM treatment. The results are shown as fold values relative to GAPDH. c The Mek inhibitor U0126 suppresses stimCM-induced Erk1/2 phosphorylation, while also modifying phosphorylation of p38 and degradation of Ikappa B-alpha. Other inhibitors, SB203580 and SN50, have minimal effects on phosphorylation of Erk1/2 (control: DMEM; LPS: DMEM supplemented with LPS). d Inhibition of Erk1/2 phosphorylation leads to lessened expression of TNF-alpha, IL-1beta, Ccl-2, Ccl-5, and Cxcl-10 in a dose-dependent manner (n = 3)