Study on the mechanism of PM2.5 affecting Th1/Th2 immune imbalance through the notch signaling pathway in asthmatic mice

• Published in: Toxicology research (Cambridge) Vol. 12; no. 4; pp. 675 - 684
• Main Authors: Wu, Ji-rong, He, Zheng, Bao, Hai-rong, Zeng, Xiao-li, Liu, Xiao-ju
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.08.2023
• Subjects: Th1/Th2; immune imbalance; Notch1; PM2.5; signaling pathway; Hes1; asthma
• ISSN: 2045-452X; 2045-4538; 2045-4538
• DOI: 10.1093/toxres/tfad044

Abstract Some research has shown that PM2.5 causes Th1/Th2 immune imbalance and aggravates asthma. However, the exact mechanism of PM2.5 causing aggravation of asthma remains unclear. The purpose of this study was to investigate whether exposure to PM2.5 exacerbates Th1/Th2 immune imbalance through the Notch signaling pathway. Eight-week-old SPF female BALF/c mice were sensitized by ovalbumin to establish an asthma mouse model. PM2.5 exposure was carried out by aerosol inhalation of PM2.5 (510 μg/m3) after each provocation. The lung function of mice was measured and Splenic T lymphocyte subsets were detected. Notch signaling pathway was tested. The levels of interferon (IFN)-γ and interleukin (IL)-4 in serum and bronchoalveolar lavage fluid were determined. The results showed that the expression of the mRNA and protein of Notch1 and Hes1 in the asthma group were significantly higher than those in healthy controls. The levels of IL-4 were also remarkably high; while the levels of IFN-γ were remarkably low in serum and BALF, the Th1% and Th1/Th2 ratios were significantly lower, and Th2% was significantly higher in the asthma group than in the healthy controls. PM2.5 promoted further activation of the Notch signaling pathway and aggravated Th1/Th2 immune imbalance in asthmatic mice. γ-secretase inhibitor can partially inhibit the activation of the Notch signaling pathway and alleviate aggravation of immune imbalance. In conclusion, the asthmatic mice had a Th1/Th2 immune imbalance and an overactivated Notch signaling pathway. PM2.5 further aggravated Th1/Th2 immune imbalance by activating the Notch signaling pathway.