Both lead (Pb) and lipopolysaccharide (LPS) damage nervous system, partly, by the induction of tumor necrosis factor-alpha (TNF-alpha) in glia origin. In this study, we examined the Pb- and LPS-triggered signal leading to TNF-alpha 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-alpha expression in U-373MG cells. Suppressing PKC by chelerythrine chloride completely diminished the Pb- and LPS-induced TNF-alpha 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-alpha expression in glial cells.
