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Liver kinase B1 (LKB1) reduced inflammation and oxidative stress by regulating the AMPK/NLRP3 signaling pathway in LPS-induced lung injury

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Abstract

Background

Inflammation and oxidative stress-induced molecular death are one of the important causes for lung injury in critically ill patients. LKB1 is an important protein kinase in the body and has regulated inflammation and oxidative stress. However, LKB1 control inflammation and oxidative stress in lung injury were unclear.

Objective

We aimed to investigate the function and mechanism of Liver kinase B1 (LKB1) in lipopolysaccharide (LPS)-induced lung injury.

Result

LKB1 prevented lung injury, and weakened correlation oxidative stress and inflammatory reaction in LPS-induced mice model of lung injury. Up-regulation of LKB1 reduced reactive oxygen species (ROS) production and it-induced oxidative stress, and weakened inflammatory reactions in LPS-induced lung injury A549 cells. Down-regulation of LKB1 increased ROS production and it-induced oxidative stress, and enhanced inflammatory reactions in LPS-induced lung injury A549 cells. LKB1 induced phosphorylation (p)-AMPK protein expression, and suppressed the protein expression of NLRP3 in LPS-induced mice model of lung injury and in LPS-induced lung injury A549 cells. This experiment demonstrated the inhibition of AMPK or activation of NLRP3 inflammasome reversed the anti-inflammation function of LKB1 in LPS-induced lung injury. Meanwhile, ROS-induced oxidative stress also participated in the anti-inflammation effects of LKB1 in LPS-induced lung injury.

Conclusion

Therefore, our results indicate that LKB1 reduced inflammation and oxidative stress by regulating the AMPK/NLRP3 signaling pathway in LPS-induced lung injury.

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Data availability

The datasets used or analysed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Anesthesiology, Zibo Central Hospital, Zibo, 255000, Shandong, China

    Yifeng Yue, Liwu Zong, Nianhai Feng, Junxia Tang & Hongyu Xu

  2. Department of Anesthesiology, People’s Hospital of Weifang Binhai Economic and Technological Development Zone, Weifang, 262737, Shandong, China

    Yongmin Chen

  3. Department of Critical Care Medicine, Zibo Central Hospital, No. 54 Gongqingtuan West Road, Zhangdian District, Zibo, 255000, Shandong, China

    Meiling Zhao

Authors
  1. Yifeng Yue
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  2. Liwu Zong
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  3. Yongmin Chen
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  4. Nianhai Feng
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  5. Junxia Tang
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  6. Hongyu Xu
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  7. Meiling Zhao
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Contributions

Guarantor of integrity of the entire study: YY; MZ. Study concepts: YY; MZ. Study design: YY; MZ. Definition of intellectual content: YY; MZ. Literature research: YY; MZ. Clinical studies: YY; LZ; YC; NF; JT; HX. Experimental studies: YY; MZ. Data acquisition: YC; HX. Data analysis: YC; HX. Statistical analysis: MZ; NF; JT. Manuscript preparation: YY; MZ; LZ. Manuscript editing: YY; MZ; LZ. Manuscript review: YY; MZ; LZ.

Corresponding author

Correspondence to Meiling Zhao.

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Conflicts of interest

Yifeng Yue, Liwu Zong, Yongmin Chen, Nianhai Feng, Junxia Tang, Hongyu Xu and Meiling Zhao declare that they have no competing interests.

Ethical approval

This study was approved by the Institutional Animal Care and Use Committee of Zibo Central Hospital.

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Yue, Y., Zong, L., Chen, Y. et al. Liver kinase B1 (LKB1) reduced inflammation and oxidative stress by regulating the AMPK/NLRP3 signaling pathway in LPS-induced lung injury. Mol. Cell. Toxicol. 17, 385–395 (2021). https://doi.org/10.1007/s13273-021-00142-9

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  • DOI: https://doi.org/10.1007/s13273-021-00142-9

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