Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai 200030, China.
Department of Anesthesiology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, No.270 Dongan Road, Shanghai 200032, China.
Ecotoxicol Environ Saf. 2019 Apr 30;171:467-474. doi: 10.1016/j.ecoenv.2019.01.005. Epub 2019 Jan 9.
Ambient particulate matter (PM) poses a great threat to global health and contributes to pulmonary inflammation. However, the potential mechanism of PM-induced inflammation of the lung remains unclear. Osteopontin (OPN) is a multifunctional protein that reportedly regulates inflammatory responses in different diseases. Here, we explored the expression of OPN with PM exposure in vivo and in vitro and attempted to elucidate the regulatory role of OPN in PM-induced airway inflammation. Our results showed that PM exposure increased the expression of OPN in the bronchial epithelium, serum, and bronchoalveolar lavage fluid (BALF) of mice. Moreover, PM induced OPN expression in human bronchial epithelial cells (HBECs) in a dose and time-dependent manner. In vitro, inflammatory cytokines such as IL-1α and IL-1β were increased in HBECs with PM exposure via the ERK and JNK signaling pathways. Recombinant human OPN could potentiate PM-induced expression of IL-1α and IL-1β, while OPN siRNA could alleviate PM-induced inflammatory responses in HBECs. Furthermore, we showed that OPN regulated PM-induced inflammatory cytokines via the ERK and JNK pathways in HBECs. This study shows for the first time the positive effect of OPN on PM-induced airway inflammation and contributes to a better understanding of its potential mechanism of action.
环境颗粒物 (PM) 对全球健康构成巨大威胁，并导致肺部炎症。然而，PM 引起肺部炎症的潜在机制尚不清楚。骨桥蛋白 (OPN) 是一种多功能蛋白，据报道它可调节不同疾病中的炎症反应。在这里，我们研究了 OPN 在体内和体外暴露于 PM 下的表达情况，并试图阐明 OPN 在 PM 诱导的气道炎症中的调节作用。我们的结果表明，PM 暴露会增加小鼠支气管上皮细胞、血清和支气管肺泡灌洗液 (BALF) 中 OPN 的表达。此外，PM 以剂量和时间依赖的方式诱导人支气管上皮细胞 (HBEC) 中 OPN 的表达。在体外，PM 通过 ERK 和 JNK 信号通路增加 HBEC 中白细胞介素-1α (IL-1α) 和白细胞介素-1β (IL-1β) 等炎症细胞因子的表达。重组人 OPN 可增强 PM 诱导的 IL-1α 和 IL-1β 的表达，而 OPN siRNA 可减轻 PM 诱导的 HBEC 炎症反应。此外，我们表明 OPN 通过 ERK 和 JNK 途径调节 HBEC 中 PM 诱导的炎症细胞因子。本研究首次显示 OPN 对 PM 诱导的气道炎症具有积极作用，有助于更好地理解其潜在的作用机制。
