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Growth arrest-specific protein 7 regulates the murine M1 alveolar macrophage polarization

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Abstract

Growth arrest-specific gene 7 (Gas7) is preferentially expressed in terminally differentiated brain cells and plays a crucial role during neuronal development and neurite outgrowth. Apart from that, Gas7 was found to be abundantly expressed in immune cells like murine macrophage without knowing the actual roles in immune reaction. By using the Illumina microarray analysis, we observed a clear induction of Gas7 but no other Gas family members in murine M1-polarized alveolar macrophage, which was further confirmed by RT-qPCR, Western blotting, and immunostaining analysis, suggesting a likelihood that Gas7 may participate in murine alveolar macrophage polarization. Moreover, we found that the upregulation of Gas7 in M1-polarized alveolar macrophage was almost fully blocked by IKK selective inhibitor BMS, which links Gas7 induction to nuclear factor kappa beta (NF-κB) signaling activation. Interestingly, we found that Gas7 knockdown by small interfering RNA transfection did not affect the pro-inflammatory cytokine gene Tnf and Ilb expression, whereas the expressions of canonic M1 marker gene Nos2 and other M1-dependent genes Il12b, Il6, Cxcl1, Cxcl2, and Cxcl9 were found to be reduced. Furthermore, Gas7-related M1 gene expression in alveolar macrophage was not dependent on NF-κB and STAT1 pathway. Our results demonstrate that Gas7 is potentially involved in regulation of murine M1 alveolar macrophage polarization.

Highlights

  • Gas7 was induced in LPS/IFNγ mediated M1 polarization.

  • Gas7 are induced during time course of M1 polarization.

  • Gas7 upregulation was dependent on NF-κB pathway in M1 polarized AMs.

  • Gas7 knockdown reduced the M1 markers gene expression in M1 polarized AMs.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81470931, 31401188) and Sichuan University 985 Project-Science and Technology Innovation Platform for Novel Drug Development.

Contributors

Conception and experiment design, acquisition of data, discussion of data, interpretation and analysis of data: Q.X., X.L., X.W., Y.H., and S.C.; writing the manuscript and revising it critically for the important intellectual content: X.W., J.C., J.L., Y.W., M.I., T.S., S.C., and N.H. All authors approved the final version to be published.

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Authors and Affiliations

  1. Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu, 610041, China

    Qian Xu, Xiaofan Liu, Xinyuan Wang, Yuanqi Hua, Xiaoying Wang, Junli Chen, Jingyu Li, Yi Wang, Shanze Chen & Ning Huang

  2. Comprehensive Pneumology Center (CPC), Institute of Lung Biology and Disease, Helmholtz Zentrum München, Neuherberg, Germany

    Tobias Stoeger

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  1. Qian Xu
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Correspondence to Shanze Chen or Ning Huang.

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The study was approved by the ethics committee of West China College of Preclinical Sciences and Forensic Medicine, Sichuan University.

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Xu, Q., Liu, X., Wang, X. et al. Growth arrest-specific protein 7 regulates the murine M1 alveolar macrophage polarization. Immunol Res 65, 1065–1073 (2017). https://doi.org/10.1007/s12026-017-8948-5

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  • DOI: https://doi.org/10.1007/s12026-017-8948-5

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