Enhancement of TNF-alpha expression does not trigger apoptosis upon exposure of glial cells to lead and lipopolysaccharide.
Lead (Pb) and lipopolysaccharide (LPS) affect not only neurons but also glial cells, and cause neurological impairment in the brain. We have previously shown an enhancement of tumor necrosis factor-alpha (TNF-alpha) in U-373MG glial cells after exposure of Pb and LPS. To determine whether Pb- or LPS-induced TNF-alpha triggers glial cell death, the apoptotic response was investigated in glial cells both in vitro and in vivo. In vitro, Pb ranging from 0.1 to 10 microM increased the expression of TNF-alpha in a dose-dependent manner in U-373MG cells. Similarly, LPS (500 ng/ml) stimulated TNF-alpha expression in the same cells. A combination of LPS and Pb did not cause higher mRNA TNF-alpha expression than LPS or Pb alone. However, exposure to Pb and LPS did not affect apoptosis in U-373MG cells detected by flow cytometric analysis with merocyanine 540 staining and propidium iodine staining. In B6 mice, glial cells in the brain were immunostained positive for TNF-alpha after an intraperitoncal administration of Pb (12.5 mg/kg) or LPS (10 mg/kg). Consistent with the findings in the cell culture system, few apoptotic cells were detected in glial and neurons by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) in the brain of B6 mice. We conclude that induction of TNF-alpha alone by Pb and LPS does not cause cell apoptosis in cells of glial origin.
Cheng
Yu-Jung
YJ
Graduate Institute of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
Yang
Bei-Chang
BC
Hsieh
Wen-Chuan
WC
Huang
Bu-Miin
BM
Liu
Ming-Yie
MY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004347:Drug Interactions; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D007854:Lead / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009457:Neuroglia / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007854:Lead