title: Microgravity activates p38 MAPK-C/EBPβ pathway to regulate the expression of arginase and inflammatory cytokines in macrophages.
abstract: OBJECTIVE
  Molecular mechanisms of microgravity-caused immunosuppression are not fully elucidated. In the present study, we investigated the effects of simulated microgravity on macrophage functions and tried to identify the related intracellular signal pathways.
  
  
  METHODS
  Primary mouse macrophages were used in the present study. The gene expression and function of IL-4-treated mouse macrophages were detected after simulated microgravity or 1 g control.
  
  
  METHODS
  Freshly isolated primary mouse macrophages were cultured in a standard simulated microgravity situation using a rotary cell culture system (RCCS-1) and 1 g control conditions. Real-time PCR, western blots and flow cytometry were used to investigate the related intracellular signals and molecule expression.
  
  
  RESULTS
  The arginase mRNA and protein levels in freshly isolated primary mouse macrophages under simulated microgravity using RCCS-1 were significantly higher than those under normal gravity. Meanwhile, simulated microgravity induced over-expression of C/EBPβ, a transcription factor of arginase promoter, and activation of p38 MAPK, which could increase C/EBPβ expression. Furthermore, up-regulation of Interleukin-6 (IL-6) and down-regulation of IL-12 p40 (IL-12B) in LPS-stimulated macrophages were also detected after simulated microgravity, which is regulated by C/EBPβ.
  
  
  CONCLUSIONS
  Simulated microgravity activates a p38 MAPK-C/EBPβ pathway in macrophages to up-regulate arginase and IL-6 expression and down-regulate IL-12B expression. Both increased arginase expression and decreased IL-12B expression in macrophages during inflammation could result in immunosuppression under microgravity.
authors: 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: Chongzhen
authors: C
authors: Wang
authors: Hui
authors: H
authors: Chen
authors: Haiying
authors: H
authors: Luo
authors: Linnan
authors: L
authors: Zhu
authors: Yang
authors: Y
authors: Zhao
authors: Hongling
authors: H
authors: Tian
authors: Ruoyu
authors: R
authors: Wang
authors: Peng
authors: P
authors: Shang
authors: Yong
authors: Y
authors: Zhao
mesh_terms: D000818:Animals; D001119:Arginase / Q000096:biosynthesis*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000502:physiology; D007249:Inflammation / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology; D014893:Weightlessness; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D016207:Cytokines; D048051:p38 Mitogen-Activated Protein Kinases; D001119:Arginase