TRPC6 modulates adhesion of neutrophils to airway epithelial cells via NF-κB activation and ICAM-1 expression with ozone exposure
TRPC6 modulates adhesion of neutrophils to airway epithelial cells via NF-κB activation and ICAM-1 expression with ozone exposure
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DOI：
10.1016/j.yexcr.2019.02.013
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发表时间：
2019-04-15
影响因子：
3.7
通讯作者：
Li, Jian-Hua
中科院分区：
文献类型：
--
作者：
Chen, Qing-Zi;Zhou, Yu-Bo;Li, Jian-Hua
臭氧（O-3）是空气污染的主要成分，它与哮喘受试者中以中性粒细胞内流为特征的气道炎症有关。经典瞬时受体电位6（TRPC 6）通道是近年来发现的氧化应激的靶点，参与气道炎症。然而，TRPC 6在气道上皮细胞和中性粒细胞中的调节作用尚未被详细阐明。在这项研究中，我们研究了TRPC 6的作用，中性粒细胞粘附气道上皮细胞暴露于O-3在体内和体外的方法。使用转基因小鼠，结果表明TRPC 6缺乏减弱了O-3诱导的中性粒细胞向气道上皮细胞的募集和细胞间粘附分子-1（ICAM-1）的表达。在体外，O-3诱导ICAM-1表达和中性粒细胞粘附到16 HBE细胞（人气道上皮细胞系），并通过TRPC 6沉默短发夹RNA（shRNA）和TRPC 6抑制剂乙酸落叶松酯（LA）降低。我们还证实，TRPC 6依赖性的Ca 2+内流和NF-κ B B活化在16 HBE细胞中是ICAM-1介导的中性粒细胞粘附暴露于O-3所必需的。本研究证实TRPC 6通过NF-κ B B活化和ICAM-1表达参与O-3诱导的中性粒细胞与气道上皮细胞的粘附，为防治空气污染相关的炎症性肺疾病提供了新的思路。
Ozone (O-3) 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-3 in vivo and in vitro approaches. Using transgenic mice, the results showed that TRPC6-deficiency attenuated O-3-induced neutrophil recruitment to airway epithelial cells and intercellular adhesion molecule-1 (ICAM-1) expression. In vitro, O-3 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 Ca2+ entry and NF-kappa B activation in 16HBE cells were required for ICAM-1-mediated neutrophil adhesion exposed to O-3. In conclusion, this study demonstrated the contribution of TRPC6 to O-3-induced neutrophil adhesion to airway epithelial cells via NF-kappa B activation and ICAM-1 expression, which may provide new potential concepts for preventing and treating air pollutant-related inflammatory lung diseases.