Shandong University, Jinan, China.
Eur Rev Med Pharmacol Sci. 2019 Feb;23(4):1688-1697. doi: 10.26355/eurrev_201902_17131.
We aimed to investigate whether PM2.5 has the potential to exacerbate neutrophil airway inflammation and to analyze the underlying mechanisms.
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.
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.
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.
本研究旨在探讨细颗粒物（PM2.5）是否具有加重中性粒细胞气道炎症的潜力，并分析其潜在机制。
使用大容量空气采样器（青岛崂应 2033B）于 2016 年 1 月 1 日至 12 月 21 日采集山东省烟台市的 PM2.5 样本。将 BALB/c 小鼠分为以下四组：对照组、卵清蛋白（OVA）组、低剂量 PM2.5 组和高剂量 PM2.5 组。除对照组外，其余各组均用 OVA 致敏和激发，低剂量 PM2.5 组和高剂量 PM2.5 组经鼻腔给予 PM2.5 混悬液。测量小鼠气道反应性。酶联免疫吸附试验（ELISA）试剂盒用于评估支气管肺泡灌洗液（BALF）和血清样本中白细胞介素 17（IL-17）和肿瘤坏死因子-α（TNF-α）的表达。通过细胞计数和组织学检查评估 PM2.5 诱导的气道炎症。Western blot 法评估整合素 β4（ITGB4）的蛋白表达。
随着乙酰胆碱氯化物（ACH）剂量的增加，PM2.5 暴露的哮喘小鼠的气道高反应性（AHR）逐渐加重。与其他组相比，PM2.5 组 BALF 和血清中的 IL-17 和 TNF-α 水平显著升高，两组之间存在显著差异。PM2.5 暴露加重了哮喘小鼠气道中炎症细胞浸润和黏液分泌。PM2.5 组的中性粒细胞百分比呈剂量依赖性显著升高。OVA 和 PM2.5 共同暴露抑制了 ITGB4 的表达。特别是，高剂量 PM2.5 组小鼠的 ITGB4 表达明显低于低剂量 PM2.5 组。
本研究表明，PM2.5 暴露通过上调 IL-17 和 TNF-α的表达，下调 ITGB4 的表达，加重哮喘小鼠中性粒细胞气道炎症。
