title: Microgravity inhibition of lipopolysaccharide-induced tumor necrosis factor-α expression in macrophage cells.
abstract: OBJECTIVE
  Microgravity environments in space can cause major abnormalities in human physiology, including decreased immunity. The underlying mechanisms of microgravity-induced inflammatory defects in macrophages are unclear.
  
  
  METHODS
  RAW264.7 cells and primary mouse macrophages were used in the present study. Lipopolysaccharide (LPS)-induced cytokine expression in mouse macrophages was detected under either simulated microgravity or 1g control.
  
  
  METHODS
  Freshly isolated primary mouse macrophages and RAW264.7 cells were cultured in a standard simulated microgravity situation using a rotary cell culture system (RCCS-1) and 1g control conditions. The cytokine expression was determined by real-time PCR and ELISA assays. Western blots were used to investigate the related intracellular signals.
  
  
  RESULTS
  LPS-induced tumor necrosis factor-α (TNF-α) expression, but not interleukin-1β expression, in mouse macrophages was significantly suppressed under simulated microgravity. The molecular mechanism studies showed that LPS-induced intracellular signal transduction including phosphorylation of IKK and JNK and nuclear translocation of NF-κB in macrophages was identical under normal gravity and simulated microgravity. Furthermore, TNF-α mRNA stability did not decrease under simulated microgravity. Finally, we found that heat shock factor-1 (HSF1), a known repressor of TNF-α promoter, was markedly activated under simulated microgravity.
  
  
  CONCLUSIONS
  Short-term treatment with microgravity caused significantly decreased TNF-α production. Microgravity-activated HSF1 may contribute to the decreased TNF-α expression in macrophages directly caused by microgravity, while the LPS-induced NF-κB pathway is resistant to microgravity.
authors.affiliation: Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beichen West Road 1-5, Chaoyang District, Beijing, 100101, China.
authors.forename: Chongzhen
authors.initials: C
authors.lastname: Wang
authors.forename: Haiying
authors.initials: H
authors.lastname: Luo
authors.forename: Linnan
authors.initials: L
authors.lastname: Zhu
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Zhulang
authors.initials: Z
authors.lastname: Chu
authors.forename: Hongling
authors.initials: H
authors.lastname: Tian
authors.forename: Meifu
authors.initials: M
authors.lastname: Feng
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Peng
authors.initials: P
authors.lastname: Shang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000276:immunology; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000276:immunology; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*; D014893:Weightlessness
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C490017:Hsf1 protein, mouse; C531390:Hsf2 protein, mouse; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha