Ubiquitin-specific protease 8 inhibits lipopolysaccharide-triggered pyroptosis of human bronchial epithelial cells by regulating PI3K/AKT and NF-κB pathways

Main Article Content

Lu Liu
Department of Respiratory and Critical Care Medicine, Wuxi 9th People’s Hospital Affiliated to Soochow University, Wuxi, China.

Liting Huan
Department of Internal Medicine, Zibo Municipal Hospital for Infectious Diseases, Zibo, China.

Yu Zhang
Department of Respiratory and Critical Care Medicine, Wuxi 9th People’s Hospital Affiliated to Soochow University, Wuxi, China.

Wei Wei
Department of Respiratory and Critical Care Medicine, Wuxi 9th People’s Hospital Affiliated to Soochow University, Wuxi, China.

Zhihai Chen
Department of Respiratory and Critical Care Medicine, Wuxi 9th People’s Hospital Affiliated to Soochow University, Wuxi, China.

Di Xu
Department of Respiratory and Critical Care Medicine, Wuxi 9th People’s Hospital Affiliated to Soochow University, Wuxi, China.

Xiufeng Huang
Department of Respiratory and Critical Care Medicine, Wuxi 9th People’s Hospital Affiliated to Soochow University, Wuxi, China.

Yaoxi Tan
Department of Respiratory and Critical Care Medicine, Wuxi 9th People’s Hospital Affiliated to Soochow University, Wuxi, China.

Hongxing Li
Department of Respiratory and Critical Care Medicine, Wuxi 9th People’s Hospital Affiliated to Soochow University, Wuxi, China.

Keywords

ubiquitin-specific protease 8, asthma, lipopolysaccharide, human bronchial epithelial cells, pyroptosis, inflammation, PI3K/AKT, NF-κB

Abstract

Asthma, characterized by dysfunction of airway epithelial cells, is regarded as a chronic inflammatory disorder in the airway. Ubiquitin-specific protease 8 (USP8) belongs to ubiquitin proteasome system and mediates the stability of E3 ligases. The anti-inflammatory effect of USP8 has been widely investigated in distinct diseases, while the role of USP8 in asthma remains elusive. Firstly, human bronchial epithelial cells (BEAS-2B) were treated with lipopolysaccharide, which reduced the cell viability of BEAS-2B and induced the secretion of lactate dehydrogenase (LDH). Moreover, the expression of USP8 was downregulated in BEAS-2B post lipopolysaccharide treatment. Secondly, overexpression of USP8 enhanced cell viability of lipopolysaccharide-treated BEAS-2B, and reduced the LDH secretion. USP8 overexpression also attenuated lipopolysaccharide-induced upregulation of TNF-α, IL-6, and IL-1β in BEAS-2B. Thirdly, lipopolysaccharide treatment promoted the expression of NLRP3 (NLR Family Pyrin Domain Containing 3), N-terminal domain of gasdermin D (GSDMD-N), caspase-1, IL-1β, and IL-18 in BEAS-2B, which was inhibited by USP8 overexpression. Lastly, USP8 overexpression decreased the phosphorylation of NF-κB, while it increased the phosphorylation of PI3K and AKT in lipopolysaccharide-treated BEAS-2B. In conclusion, USP8 inhibited lipopolysaccharide-triggered inflammation and pyroptosis in human bronchial epithelial cells by activating PI3K/AKT signaling and inhibiting NF-κB signaling pathway.

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Mar 1, 2022
DOI: https://doi.org/10.15586/aei.v50i2.568

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How to Cite
Liu, L., Huan, L., Zhang, Y., Wei, W., Chen, Z., Xu, D., Huang, X., Tan, Y., & Li, H. (2022). Ubiquitin-specific protease 8 inhibits lipopolysaccharide-triggered pyroptosis of human bronchial epithelial cells by regulating PI3K/AKT and NF-κB pathways. Allergologia Et Immunopathologia, 50(2), 96-103. https://doi.org/10.15586/aei.v50i2.568
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Vol. 50 No. 2 (2022): Allergologia et Immunopathologia
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Original Articles
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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

How to Cite

Liu, L., Huan, L., Zhang, Y., Wei, W., Chen, Z., Xu, D., Huang, X., Tan, Y., & Li, H. (2022). Ubiquitin-specific protease 8 inhibits lipopolysaccharide-triggered pyroptosis of human bronchial epithelial cells by regulating PI3K/AKT and NF-κB pathways. Allergologia Et Immunopathologia, 50(2), 96-103. https://doi.org/10.15586/aei.v50i2.568