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Protectin DX ameliorates inflammation in sepsis-induced acute lung injury through mediating PPARγ/NF-κB pathway

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Abstract

Previous reports have demonstrated that the newly identified lipid mediator protectin DX (PDX) could effectively attenuate multiple organ injuries in sepsis. The aim of our study was to clarify whether PDX could improve acute lung injury (ALI) induced by sepsis and elucidate the relevant potential mechanism. After inducing sepsis by the cecal ligation and puncture approach, mice were treated with a high or low dose of PDX. Pathological changes in the pulmonary tissue were analyzed by hematoxylin-eosin staining, and lung injury score was evaluated. Lung permeability and edema were assessed by lung wet/dry ratio, and protein and cellular load of the bronchoalveolar lavage fluid (BALF). Inflammatory cytokine levels in BALF were measured by ELISA and the expression of PPARγ in the lung tissue was analyzed by immunoblotting. The results suggested that PDX could diminish the inflammatory response in lung tissue after sepsis by upregulating PPARγ and inhibiting the phosphorylation and activation of NF-κB p65. PDX treatment lowered the levels of pro-inflammation cytokines IL-1β, IL-6, TNF-α, and MCP-1, and the levels of anti-inflammatory cytokine IL-10 was increased in the BALF. It also improved lung permeability and reduced lung injury. Furthermore, the protective effect of PDX on lung tissue could be reversed by GW9662, a specific PPAR-γ antagonist. Taken together, our study indicated that PDX could ameliorate the inflammatory response in ALI by activating the PPARγ/NF-κB pathway in a mouse model of sepsis.

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Funding

This study was supported by the grants from the National Natural Science Foundation of China (No.81701887; No.81671890) and the Scientific Research Projects of Hubei Education Department (B2016081).

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Author notes

  1. Haifa Xia and Yangyang Ge contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Haifa Xia, Yangyang Ge, Fuquan Wang, Zhouyang Wu, Jingxu Wang, Shujun Sun, Shiqian Huang, Ming Chen, Weimin Xiao & Shanglong Yao

  2. Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, 430022, China

    Haifa Xia, Yangyang Ge, Fuquan Wang, Zhouyang Wu, Jingxu Wang, Shujun Sun, Shiqian Huang, Ming Chen, Weimin Xiao & Shanglong Yao

  3. College of Health Science and Nursing, Wuhan Polytechnic University, Wuhan, 430023, China

    Yu Ming

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  1. Haifa Xia
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Contributions

Haifa Xia and Yangyang Geng wrote this article and performed the experiments. Fuquan Wang, Jingxu Wang, Shiqian Huang, and Ming Chen established the animal models and collected samples. Yu Ming, Zhouyang Wu, and Shujun Sun analyzed the data and prepared the figures. Weimin Xiao and Shanglong Yao designed the experiments and revised the article. All authors read and approved the final version of the manuscript.

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Correspondence to Weimin Xiao or Shanglong Yao.

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Supplementary Figure1

PDX reduced bacterial CFU counts in BALF after sepsis-induced ALI. Representative pictures of CFU counts in BALF in sham, CLP, LD-PDX, and HD-PDX groups. Data was presented as means ± SEM, n = 7. *P < 0.05 LD-PDX versus the CLP group; ##P < 0.01 HD-PDX versus the CLP group (JPG 78 kb)

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Xia, H., Ge, Y., Wang, F. et al. Protectin DX ameliorates inflammation in sepsis-induced acute lung injury through mediating PPARγ/NF-κB pathway. Immunol Res 68, 280–288 (2020). https://doi.org/10.1007/s12026-020-09151-7

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  • DOI: https://doi.org/10.1007/s12026-020-09151-7

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