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Apolipoprotein M Protects Against Lipopolysaccharide-Induced Acute Lung Injury via Sphingosine-1-Phosphate Signaling

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Abstract

It had been demonstrated that apolipoprotein M (apoM) is an important carrier of sphingosine-1-phosphate (S1P) in blood, and the S1P has critical roles in the pathogenesis of sepsis-induced acute lung injury (ALI). In the present study, we investigated whether apoM has beneficial effects in a mouse model after lipopolysaccharide (LPS)-induced ALI. Forty-eight mice were divided into two groups: male C57BL/6 wild-type (apoM+/+) group (n = 24) and apoM gene-deficient (apoM−/−) group (n = 24) and then randomly subdivided into four subgroups (n = 6 each) according to different intraperitoneal (i.p.) injection: control group, W146 group, LPS group, and LPS + W146 group. Serum levels of interleukin-1 beta (IL-1β) and mRNA levels of IL-1β, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), lung histology, wet/dry weight ratio, and immunohistochemistry were measured at 3 h after the baseline and compared in each group. Our results clearly demonstrated that IL-1β mRNA levels and other inflammatory biomarkers were significantly increased in the lungs of LPS-induced ALI apoM−/− mice compared to those of the apoM+/+ mice. Moreover, when apoM+/+ mice were treated with W146, a S1P receptor (S1PR1) antagonist, these inflammatory biomarkers could be significantly upregulated by LPS-induced ALI. Therefore, it suggests that apoM-S1P-S1PR1 signaling might underlie the pathogenesis of ALI and apoM could have physiological benefits to alleviate LPS-induced ALI.

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Funding

This work was supported by the Program of Bureau of Science and Technology Foundation of Changzhou (CJ20159022), Major Science and Technology Project of Changzhou Municipal Commission of Health and Family Planning (ZD201505), and “333 Project” (BRA2016122) of Jiangsu Province. Dr. Bin Zhu was supported by the Program of Health Top-notch Talent of Changzhou City and Youth Medical Talent of Jiangsu Province.

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Authors and Affiliations

  1. Department of Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213003, China

    Bin Zhu

  2. Comprehensive Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213003, China

    Guang-hua Luo, Yue-hua Feng, Miao-mei Yu, Jun Zhang & Jiang Wei

  3. Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, China

    Chun Yang

  4. Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, 221 85, Lund, Sweden

    Ning Xu

  5. Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, Jiangsu Province, 213003, China

    Xiao-ying Zhang

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  1. Bin Zhu
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Animal care was in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and was approved by the Animal Use and Protection Committee of Soochow University.

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Zhu, B., Luo, Gh., Feng, Yh. et al. Apolipoprotein M Protects Against Lipopolysaccharide-Induced Acute Lung Injury via Sphingosine-1-Phosphate Signaling. Inflammation 41, 643–653 (2018). https://doi.org/10.1007/s10753-017-0719-x

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