Both lead (Pb) and lipopolysaccharide (LPS) damage nervous system, partly, by the induction of tumor necrosis factor-α (TNF-α) in glia origin. In this study, we examined the Pb- and LPS-triggered signal leading to TNF-α expression in a glioma cell line, U-373MG. Both Pb and LPS increased the phosphorylation of p42/44 mitogen-activated protein kinase (MAPK), which depended on the activation of MAPK kinase (MEK) and protein kinase C (PKC). Selective p42/44 MAPK inhibitor could reduce the Pb- and LPS-triggered TNF-α expression in U-373MG cells. Suppressing PKC by chelerythrine chloride completely diminished the Pb- and LPS-induced TNF-α expression in glial cells in the mouse brain. Thus, our results indicated that PKC-MEK-p42/44 MAPK is a common signaling pathway for Pb- and LPS-induced TNF-α expression in glial cells.
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