title: Lipopolysaccharide (LPS) potentiates hydrogen peroxide toxicity in T98G astrocytoma cells by suppression of anti-oxidative and growth factor gene expression.
abstract: BACKGROUND
  Lipopolysaccharide (LPS) is a cell wall component of Gram-negative bacteria with proved role in pathogenesis of sepsis. Brain injury was observed with both patients dead from sepsis and animal septic models. However, in vitro administration of LPS has not shown obvious cell damage to astrocytes and other relative cell lines while it does cause endothelial cell death in vitro. These observations make it difficult to understand the role of LPS in brain parenchymal injury.
  
  
  RESULTS
  To test the hypothesis that LPS may cause biological changes in astrocytes and make the cells to become vulnerable to reactive oxygen species, a recently developed highly sensitive and highly specific system for large-scale gene expression profiling was used to examine the gene expression profile of a group of 1,135 selected genes in a cell line, T98G, a derivative of human glioblastoma of astrocytic origin. By pre-treating T98G cells with different dose of LPS, it was found that LPS treatment caused a broad alteration in gene expression profile, but did not cause obvious cell death. However, after short exposure to H2O2, cell death was dramatically increased in the LPS pretreated samples. Interestingly, cell death was highly correlated with down-regulated expression of antioxidant genes such as cytochrome b561, glutathione s-transferase a4 and protein kinase C-epsilon. On the other hand, expression of genes encoding growth factors was significantly suppressed. These changes indicate that LPS treatment may suppress the anti-oxidative machinery, decrease the viability of the T98G cells and make the cells more sensitive to H2O2 stress.
  
  
  CONCLUSIONS
  These results provide very meaningful clue for further exploring and understanding the mechanism underlying astrocyte injury in sepsis in vivo, and insight for why LPS could cause astrocyte injury in vivo, but not in vitro. It will also shed light on the therapeutic strategy of sepsis.
authors.affiliation: Department of Molecular Genetics, Microbiology and Immunology/The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. yue@umdnj.edu
authors.forename: Gang
authors.initials: G
authors.lastname: Yue
authors.forename: Guanfang
authors.initials: G
authors.lastname: Shi
authors.forename: Marco A
authors.initials: MA
authors.lastname: Azaro
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
authors.forename: Guohong
authors.initials: G
authors.lastname: Hu
authors.forename: Minjie
authors.initials: M
authors.lastname: Luo
authors.forename: Kingsley
authors.initials: K
authors.lastname: Yin
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nagele
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Fine
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Yang
authors.forename: Honghua
authors.initials: H
authors.lastname: Li
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001254:Astrocytoma; D016923:Cell Death; D045744:Cell Line, Tumor; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D018805:Sepsis / Q000378:metabolism
chemical_list: D000975:Antioxidants; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D006861:Hydrogen Peroxide