Regulation of tumor necrosis factor-alpha in glioma cells by lead and lipopolysaccharide: involvement of common signaling pathway.
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.
Department of Gynecology and Obstetrics, Sin-Lau Christian Hospital, Tainan 701, Taiwan.
Yu-Jung
YJ
Cheng
Ming-Yie
MY
Liu
Tung-Pi
TP
Wu
Bei-Chang
BC
Yang
D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007854:Lead / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D010617:Phenanthridines / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D010617:Phenanthridines; D014409:Tumor Necrosis Factor-alpha; D007854:Lead; C016299:chelerythrine; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases