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Particulate matter 2.5 triggers airway inflammation and bronchial hyperresponsiveness in mice by activating the SIRT2-p65 pathway / 医学前沿
Frontiers of Medicine ; (4): 750-766, 2021.
Article in English | WPRIM | ID: wpr-922505
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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Full text: Available Index: WPRIM (Western Pacific) Main subject: Signal Transduction / NF-kappa B / Transcription Factor RelA / Particulate Matter / Sirtuin 2 / Inflammation Limits: Animals Language: English Journal: Frontiers of Medicine Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Signal Transduction / NF-kappa B / Transcription Factor RelA / Particulate Matter / Sirtuin 2 / Inflammation Limits: Animals Language: English Journal: Frontiers of Medicine Year: 2021 Type: Article