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Inamm. Res. (2015) 64:303311DOI 10.1007/s00011-015-0811-3 Inammation Research
ORIGINAL RESEARCH PAPER
Microgravity activates p38 MAPK-C/EBPb pathway to regulate the expression of arginase and inammatory cytokinesin macrophages
Chongzhen Wang1,2 Hui Chen1 Haiying Luo1 Linnan Zhu1 Yang Zhao1
Hongling Tian1,3 Ruoyu Wang3 Peng Shang4 Yong Zhao1
Received: 4 March 2014 / Revised: 24 January 2015 / Accepted: 10 February 2015 / Published online: 25 March 2015 Springer Basel 2015
AbstractObjective and design Molecular mechanisms of micro-gravity-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. Material or subjects 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 ow
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 signicantly higher than those under normal gravity. Meanwhile, simulated micro-gravity induced over-expression of C/EBPb, a transcription factor of arginase promoter, and activation of p38 MAPK, which could increase C/EBPb 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/EBPb.
Conclusions Simulated microgravity activates a p38 MAPK-C/EBPb 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 inammation could result in immunosuppression under microgravity.
Keywords Microgravity Macrophages Arginase I
C/EBPb p38 MAPK Interleukin-12
Introduction
Microgravity exposure could cause severe abnormalities in human physiology, including uid shift, anemia, osteoporosis, immunosuppression, etc. [13]. In the 1960s and 1970s, 15 of the 29 Apollo astronauts reported bacterial or viral infections that occurred during ight or soon after return to earth [4]. Subsequent in-ight studies indicated that spaceight was specically associated with the reactivation of latent herpes viruses [511], which is indicative
Responsible Editor: Mauro Teixeira.
C. Wang and H. Chen have contributed equally as the...