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Microgravity inhibition of lipopolysaccharide-induced tumor necrosis factor-α expression in macrophage cells

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Abstract

Objective and design

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.

Material or subjects

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.

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Acknowledgments

We thank Dr. Chenming Sun for his review of the manuscript, Mrs Jianxia Peng and Mrs. Xiaoqiu Liu for expert technical assistance, Mrs. Yanli Hao for excellent laboratory management, and Mr. Hongfei Wu for outstanding animal husbandry. This work was supported by grants from the National Basic Research Program of China (2011CB710903, 2010CB945301, YZ) and the National Natural Science Foundation for general and Key Programs (C81130055, U0832003, YZ).

Conflict of interest

The authors declare no conflict of interests.

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Authors and Affiliations

  1. 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

    Chongzhen Wang, Haiying Luo, Linnan Zhu, Fan Yang, Zhulang Chu, Hongling Tian, Meifu Feng & Yong Zhao

  2. Key Laboratory for Space Bioscience and Biotechnology, Faculty of Life Sciences, Northwestern Polytechnical University, 127 Youyi Xilu, Xi’an, 710072, Shanxi, China

    Peng Shang

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  1. Chongzhen Wang
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  2. Haiying Luo
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  3. Linnan Zhu
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  4. Fan Yang
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  5. Zhulang Chu
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  6. Hongling Tian
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  7. Meifu Feng
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  8. Yong Zhao
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  9. Peng Shang
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Corresponding authors

Correspondence to Yong Zhao or Peng Shang.

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Responsible Editor: Michael J. Parnham.

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Wang, C., Luo, H., Zhu, L. et al. Microgravity inhibition of lipopolysaccharide-induced tumor necrosis factor-α expression in macrophage cells. Inflamm. Res. 63, 91–98 (2014). https://doi.org/10.1007/s00011-013-0676-2

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  • DOI: https://doi.org/10.1007/s00011-013-0676-2

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