Study on the mechanism of PM2.5 affecting Th1/Th2 immune imbalance through the notch signaling pathway in asthmatic mice
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Ji-Rong Wu1, Zheng He1, Hai-Rong Bao1
1Department of Grontal Respiratory Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, China.
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.
Insights
Particulate matter (PM2.5) exposure worsens asthma by activating the Notch signaling pathway, leading to immune imbalance. Inhibiting this pathway can help alleviate asthma symptoms.
Area of Science:
- Immunology
- Environmental Health
- Molecular Biology
Background:
- Particulate matter (PM2.5) is linked to asthma exacerbation.
- The precise mechanisms by which PM2.5 aggravates asthma are not fully understood.
- Th1/Th2 immune imbalance is implicated in asthma pathogenesis.
Purpose of the Study:
- To investigate if PM2.5 exacerbates Th1/Th2 immune imbalance via the Notch signaling pathway.
- To elucidate the role of Notch signaling in PM2.5-induced asthma aggravation.
Main Methods:
- Established an ovalbumin-induced asthma mouse model.
- Exposed asthmatic mice to PM2.5 via aerosol inhalation.
- Measured lung function, splenic T lymphocyte subsets, and serum/BALF cytokine levels (IFN-γ, IL-4).
- Assessed Notch signaling pathway activation (Notch1, Hes1 expression).
Main Results:
- Asthmatic mice exhibited elevated IL-4, low IFN-γ, reduced Th1/Th2 ratios, and increased Th2%.
- PM2.5 exposure further activated the Notch signaling pathway (increased Notch1 and Hes1).
- PM2.5 exposure exacerbated Th1/Th2 immune imbalance in asthmatic mice.
- A γ-secretase inhibitor partially reversed Notch pathway activation and immune imbalance.
Conclusions:
- Asthmatic mice display Th1/Th2 immune imbalance and an overactivated Notch signaling pathway.
- PM2.5 aggravates this immune imbalance by activating the Notch signaling pathway.
- Targeting the Notch pathway may offer a therapeutic strategy for PM2.5-induced asthma aggravation.
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