Key Laboratory of Protein Modification and Degradation in School of Basic Medical Sciences, Affiliated Cancer Hospital & Institute, Guangzhou Medical University, Guangzhou, China.
Key Laboratory of Protein Modification and Degradation in School of Basic Medical Sciences, Affiliated Cancer Hospital & Institute, Guangzhou Medical University, Guangzhou, China; The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Exp Cell Res. 2019 Apr 15;377(1-2):56-66. doi: 10.1016/j.yexcr.2019.02.013. Epub 2019 Feb 16.
Ozone (O) is a major component of air pollution, which has been associated with airway inflammation characterized by the influx of neutrophils in asthmatic subjects. Canonical transient receptor potential 6 (TRPC6) channel is recently identified as a target of oxidative stress which is involved in airway inflammation. However, the regulatory role of TRPC6 in airway epithelial cells and neutrophils has not yet been illuminated in detail. In this study, we investigated the role of TRPC6 in neutrophil adhesion to airway epithelial cells exposed to O in vivo and in vitro approaches. Using transgenic mice, the results showed that TRPC6-deficiency attenuated O-induced neutrophil recruitment to airway epithelial cells and intercellular adhesion molecule-1 (ICAM-1) expression. In vitro, O induced ICAM-1 expression and neutrophil adhesion to 16HBE cells (human airway epithelial cell line) and which were reduced by both TRPC6 silencing short hairpin RNA (shRNA) and TRPC6 inhibitor Larixyl Acetate (LA). We also confirmed that TRPC6-dependent Ca entry and NF-κB activation in 16HBE cells were required for ICAM-1-mediated neutrophil adhesion exposed to O. In conclusion, this study demonstrated the contribution of TRPC6 to O-induced neutrophil adhesion to airway epithelial cells via NF-κB activation and ICAM-1 expression, which may provide new potential concepts for preventing and treating air pollutant-related inflammatory lung diseases.
臭氧（O）是空气污染的主要成分，与哮喘患者气道炎症中中性粒细胞的浸润有关。最近发现，经典瞬时受体电位 6（TRPC6）通道是氧化应激的靶点，参与气道炎症。然而，TRPC6 在气道上皮细胞和中性粒细胞中的调节作用尚未详细阐明。在这项研究中，我们通过体内和体外方法研究了 TRPC6 在暴露于臭氧的气道上皮细胞中中性粒细胞黏附中的作用。使用转基因小鼠的结果表明，TRPC6 缺失减弱了臭氧诱导的中性粒细胞向气道上皮细胞的募集和细胞间黏附分子-1（ICAM-1）的表达。在体外，臭氧诱导 16HBE 细胞（人气道上皮细胞系）中 ICAM-1 的表达和中性粒细胞的黏附，这两种作用都可以通过 TRPC6 沉默短发夹 RNA（shRNA）和 TRPC6 抑制剂 Larixyl Acetate（LA）来减弱。我们还证实，臭氧暴露下，16HBE 细胞中 TRPC6 依赖性 Ca2+内流和 NF-κB 激活是 ICAM-1 介导的中性粒细胞黏附所必需的。总之，这项研究表明，TRPC6 通过 NF-κB 激活和 ICAM-1 表达促进臭氧诱导的中性粒细胞黏附到气道上皮细胞，这可能为预防和治疗与空气污染物相关的炎症性肺部疾病提供新的潜在概念。
