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Dual Regulation of Nicotine on NLRP3 Inflammasome in Macrophages with the Involvement of Lysosomal Destabilization, ROS and α7nAChR

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Abstract

Nicotine, the primary alkaloid in tobacco products, has been shown to have immunoregulatory function in at least 20 diseases. The biological mechanism of action of nicotine immunoregulation is complex, resulting in an improvement of some disease states and exacerbation of others. Given the central role of the NLRP3 inflammasome in macrophages among multiple inflammatory diseases, this study examined how nicotine alters NLRP3 inflammasome activation in macrophages. NLRP3 inflammasome activation was examined mechanistically in the context of different nicotine dosages. We show NLRP3 inflammasome activation, apoptosis-associated speck-like protein (ASC) expression, caspase-1 activity and subsequent IL-1β secretion were positively correlated with nicotine in a dose-dependent relationship, and destabilization of lysosomes and ROS production were also involved. At high concentrations of nicotine surpassing 0.25 mM, NLRP3 inflammasome activity declined, along with increased expression of the anti-inflammatory Alpha7 nicotinic acetylcholine receptor (α7nAChR) and the inhibition of TLR4/NF-κB signaling. Consequently, high doses of nicotine also reduced ASC expression, caspase-1 activity and IL-1β secretion in macrophages. Collectively, these results suggest a dual regulatory function of nicotine on NLRP3 inflammasome activation in macrophages, that is involved with the pro-inflammatory effects of lysosomal destabilization and ROS production. We also show nicotine mediates anti-inflammatory effects by activating α7nAChR at high doses.

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Data Availability

The data in this study is available from the corresponding author upon reasonable request.

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Acknowledgements

We express our sincere gratitude to Professor Cong-yi Wang (The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology) for his revision of the English in this paper.

Funding

This research was financially supported by the Key Laboratory of Tobacco Biological Effects (Grant NO.110202102011)

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Authors and Affiliations

  1. China National Tobacco Quality Supervision & Test Center, No. 2 Fengyang Street, Zhengzhou, 450001, Henan, China

    Xiaqing Wu, Yushan Tian, Hongjuan Wang, Huan Chen, Hongwei Hou & Qingyuan Hu

  2. Key Laboratory of Tobacco Biological Effects, No. 2 Fengyang Street, Zhengzhou, 450001, Henan, China

    Xiaqing Wu, Yushan Tian, Hongjuan Wang, Huan Chen, Hongwei Hou & Qingyuan Hu

  3. Beijing Life Science Academy, Lutuan East Road, Beijing, 102200, China

    Xiaqing Wu, Yushan Tian, Hongjuan Wang, Huan Chen, Hongwei Hou & Qingyuan Hu

  4. Key Laboratory of Tobacco Biological Effects and Biosynthesis, Lutuan East Road, Beijing, 102200, China

    Xiaqing Wu, Yushan Tian, Hongjuan Wang, Huan Chen, Hongwei Hou & Qingyuan Hu

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  1. Xiaqing Wu
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Contributions

Xiaqing Wu, Yushan Tian, and Hongjuan Wang designed experiments. Xiaqing Wu and Yushan Tian carried out experiments. Xiaqing Wu performed the data collection and analysis. Xiaqing Wu drafted this manuscript. Huan Chen, Hongwei Hou, and Qingyuan Hu performed the language modification. All authors have read and approved the final manuscript.

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Correspondence to Hongwei Hou or Qingyuan Hu.

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Wu, X., Tian, Y., Wang, H. et al. Dual Regulation of Nicotine on NLRP3 Inflammasome in Macrophages with the Involvement of Lysosomal Destabilization, ROS and α7nAChR. Inflammation (2024). https://doi.org/10.1007/s10753-024-02036-z

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