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RAGE deficiency attenuates the protective effect of Lidocaine against sepsis-induced acute lung injury

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Abstract

Lidocaine (Lido) is reported to suppress inflammatory responses and exhibit a therapeutic effect in models of cecal ligation and puncture (CLP)-induced acute lung injury (ALI). The receptor for advanced glycation end product (RAGE) exerts pro-inflammatory effects by enhancing pro-inflammatory cytokine production. However, the precise mechanism by which Lido confers protection against ALI is not clear. ALI was induced in RAGE WT and RAGE knockout (KO) rats using cecal ligation and puncture (CLP) operations for 24 h. The results showed that Lido significantly inhibited CLP-induced lung inflammation and histopathological lung injury. Furthermore, Lido significantly reduced CLP-induced upregulation of HMGB1 and RAGE expression and activation of the NF-κB and MAPK signaling pathways. With the use of RAGE KO rats, we demonstrate here that RAGE deficiency attenuates the protective effect of Lido against CLP-induced lung inflammatory cell infiltration and histopathological lung injury. These results suggest that RAGE deficiency attenuates the protective effect of Lido against CLP-induced ALI by attenuating the pro-inflammatory cytokines production.

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Author’s Contributions

ZZ, JZ, CL, XL, ML, DS, and XJ conceptualize, design, analyze, and interpret the data and wrote the manuscript.

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Authors and Affiliations

  1. Department of Pharmacology, Pharmacy College of Southwest Medical University, Luzhou, Sichuan, China

    Zhuo Zhang, Xiaobing Li, Minghua Liu & Daqiang Song

  2. Department of Traditional Chinese Pharmacology, Pharmacy College of Southwest Medical University, Luzhou, Sichuan, China

    Jie Zhou

  3. Department of Anesthesiology, the First Affiliated Hospital of Southwest Medical University, No.319 Zhongshan Road, Luzhou, Sichuan, China

    Changli Liao & Xian Jiang

Authors
  1. Zhuo Zhang
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  2. Jie Zhou
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  3. Changli Liao
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  4. Xiaobing Li
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  5. Minghua Liu
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  7. Xian Jiang
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Correspondence to Xian Jiang.

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Zhang, Z., Zhou, J., Liao, C. et al. RAGE deficiency attenuates the protective effect of Lidocaine against sepsis-induced acute lung injury. Inflammation 40, 601–611 (2017). https://doi.org/10.1007/s10753-016-0507-z

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  • DOI: https://doi.org/10.1007/s10753-016-0507-z

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