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

doi:10.1007/s11684-021-0839-4

Frontiers of Medicine

2021, Vol. 15

Issue (5): 750-766 https://doi.org/10.1007/s11684-021-0839-4

本期目录

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

Manling Liu¹, Zhaoling Shi², Yue Yin¹, Yishi Wang¹, Nan Mu¹, Chen Li¹(

), Heng Ma¹(

), Qiong Wang³(

)

¹. Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi’an 710032, China
². Department of Pediatrics, Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712046, China
³. Department of Cardiovascular Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China

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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.

Key words： particulate matter 2.5 sirtuin 2 p65 airway inflammation bronchial hyperresponsiveness triptolide

收稿日期: 2020-07-13 出版日期: 2021-11-01

Corresponding Author(s): Chen Li,Heng Ma,Qiong Wang

引用本文:

. [J]. Frontiers of Medicine, 2021, 15(5): 750-766.
Manling Liu, Zhaoling Shi, Yue Yin, Yishi Wang, Nan Mu, Chen Li, Heng Ma, Qiong Wang. Particulate matter 2.5 triggers airway inflammation and bronchial hyperresponsiveness in mice by activating the SIRT2--p65 pathway. Front. Med., 2021, 15(5): 750-766.

链接本文:

https://academic.hep.com.cn/fmd/CN/10.1007/s11684-021-0839-4
https://academic.hep.com.cn/fmd/CN/Y2021/V15/I5/750

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