Dose dependency PM2.5 aggravated airway inflammation in asthmatic mice via down-regulating expression of ITGB4

P.-F. Yu, L.-L. Pang, Q.-S. Mao, S.-C. Zou, Y. Shi, D.-J. Lin

Shandong University, Jinan, China. dr_lindianjie_208@163.com

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• Respiratory Medicine

OBJECTIVE: We aimed to investigate whether PM2.5 has the potential to exacerbate neutrophil airway inflammation and to analyze the underlying mechanisms.

MATERIALS AND METHODS: The high-volume air sampler (Laoying 2033B, Qingdao, China) was used to collect PM2.5 from January 01, 2016 to December 21, 2016 in Yantai, Shandong Province, China. BALB/c mice were divided into the following four groups: control group, ovalbumin (OVA) group, low-dose PM2.5 group and high-dose PM2.5 group. Mice except for control group were sensitized and challenged by OVA, and those in low-dose PM2.5 group and high-dose PM2.5 group were intranasally administered by PM2.5 suspension. Airway responsiveness of mice was measured. Enzyme-linked immunosorbent assay (ELISA) kit was used to evaluate the expressions of interleukin 17 (IL-17) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) and serum samples. Cell counting in BALF and histological examination were measured to explore PM2.5-induced airway inflammation. Protein expression of Integrin β4 (ITGB4) was assessed by Western blot.

RESULTS: Airway hyperresponsiveness (AHR) exacerbated in PM2.5 exposed asthmatic mice in progressively increased doses of acetylcholine chloride (ACH). Levels of IL-17 and TNF-αin BALF and serum increased significantly in PM2.5 groups compared with other groups with significant differences between two PM2.5 groups. PM2.5 exposure exacerbated inflammatory cell infiltration and mucus secretion in airways of asthmatic mice. Percentage of neutrophils in PM2.5 groups was significantly higher in dose-dependent manner. OVA and PM2.5 co-exposure inhibited the expression of ITGB4. In particular, ITGB4 expression in mice of high-dose PM2.5 group was significantly lowered than the low-dose PM2.5 group.

CONCLUSIONS: We showed that PM2.5 exposure exacerbates neutrophil airway inflammation in asthmatic mice though up-regulating expressions of IL-17 and TNF-α but down-regulating the expression of ITGB4.

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