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Particulate matter 2.5 triggers airway inflammation and bronchial hyperresponsiveness in mice by activating the SIRT2-p65 pathway

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Abstract

Exposure to particulate matter 2.5 (PM2.5) potentially triggers airway inflammation by activating nuclear factor-κB (NF-κB). Sirtuin 2 (SIRT2) is a key modulator in inflammation. However, the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied. Therefore, this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues. Subsequently, SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway. The activation of p65 triggered airway inflammation, increment of mucus secretion by goblet cells, and acceleration of tracheal stenosis. Meanwhile, p65 phosphorylation and acetylation, airway inflammation, and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5. Triptolide (a specific p65 inhibitor) reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure. Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.

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Acknowledgements

This work was supported by the following grants: National Natural Science Foundation of China (Nos. 31671424, 91749108, and 81322004 to Heng Ma; No. 81200036 to Manling Liu); the Science and Technology Research and Development Program of Shaanxi Province, China (No. 2015KW-050 to Heng Ma, No. 2019SF-008 to Manling Liu, and No. 2018SF-101 to Nan Mu); and the Youth Innovation Team of Shaanxi Universities, China (to Heng Ma, Yue Yin, Nan Mu, Yishi Wang). Language Editorial Service were provided by Freescience Information Technology Co., Ltd. (Ningbo, China).

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Correspondence to Chen Li, Heng Ma or Qiong Wang.

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Manling Liu, Zhaoling Shi, Yue Yin, Yishi Wang, Nan Mu, Chen Li, Heng Ma, and Qiong Wang declare no competing interests. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Liu, M., Shi, Z., Yin, Y. et al. Particulate matter 2.5 triggers airway inflammation and bronchial hyperresponsiveness in mice by activating the SIRT2-p65 pathway. Front. Med. 15, 750–766 (2021). https://doi.org/10.1007/s11684-021-0839-4

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