Journal of Translational Medicine (Aug 2017)

Glucocorticoid attenuates acute lung injury through induction of type 2 macrophage

  • Guo-wei Tu,
  • Yi Shi,
  • Yi-jun Zheng,
  • Min-jie Ju,
  • Hong-yu He,
  • Guo-guang Ma,
  • Guang-wei Hao,
  • Zhe Luo

DOI
https://doi.org/10.1186/s12967-017-1284-7
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 11

Abstract

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Abstract Background Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe inflammatory lung diseases. Methylprednisolone (MP) is a common drug against inflammation in clinic. In this study, we aim to investigate the protective effect of MP on ALI and potential mechanisms. Methods Male BABL/c mice were injected through tail vein using lipopolysaccharide (LPS, 5 mg/kg) with or without 5 mg/kg MP. Lung mechanics, tissue injury and inflammation were examined. Macrophage subsets in the lung were identified by flow cytometry. Macrophages were cultured from bone marrow of mice with or without MP. Then, we analyzed and isolated the subsets of macrophages. These isolated macrophages were then co-cultured with CD4+ T cells, and the percentage of regulatory T cells (Tregs) was examined. The expression of IL-10 and TGF-β in the supernatant was measured. The Tregs immunosuppression function was examined by T cell proliferation assay. To disclose the mechanism of the induction of Tregs by M2c, we blocked IL-10 or/and TGF-β using neutralizing antibody. Results Respiratory physiologic function was significantly improved by MP treatment. Tissue injury and inflammation were ameliorated in the MP-treated group. After MP treatment, the number of M1 decreased and M2 increased in the lung. In in vitro experiment, MP promoted M2 polarization rather than M1. We then induced M1, M2a and M2c from bone marrow cells. M1 induced more Th17 while M2 induced more CD4+CD25+Fxop3+ Tregs. Compared with M2a, M2c induced more Tregs, and this effect could be blocked by anti-IL-10 and anti-TGF-β antibodies. However, M2a and M2c have no impact on Tregs immunosuppression function. Conclusion In conclusion, MP ameliorated ALI by promoting M2 polarization. M2, especially M2c, induced Tregs without any influence on Tregs immunosuppression function.

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