Affiliation:
1. Department of Respiratory and Critical Medicine, Key Laboratory of Respiratory Disease of Ningbo The First Affiliated Hospital of Ningbo University Ningbo China
2. Department of Respiratory and Critical Care Medicine Municipal Hospital Affiliated to Taizhou University Taizhou China
Abstract
AbstractThe relationship between fine particulate matter (PM2.5) and chronic airway inflammatory diseases, such as chronic obstructive pulmonary disease and asthma, have garnered public attention, while the detailed mechanisms of PM2.5‐induced airway inflammation remain unclear. This study reveals that PM2.5 induces airway inflammation both in vivo and in vitro, and, moreover, identifies DNA damage and DNA damage repair (DDR) as results of this exposure. Ataxia telangiectasia‐mutated heterozygous (ATM+/−) and wild‐type C57BL/6 (WT) mice were exposed to PM2.5. The results show that, following exposure to PM2.5, the number of neutrophils in broncho alveolar lavage fluid and the mRNA expression of CXCL‐1 in lung tissues of the ATM+/− mice were lower than those of the WT mice. The mRNA expression of FANCD2 and FANCI were also down‐regulated. Human bronchial epithelial (HBE) cells were transfected with ATM‐siRNA to induce down‐regulation of ATM gene expression and were subsequently stimulated with PM2.5. The results show that the mRNA expression of TNF‐α decreased in the ATM‐siRNA‐transfected cells. The mRNA expression of CXCL‐1 and CXCL‐2 in peritoneal macrophages, derived from ATM‐null mice in which experiments showed that the protein expression of FANCD2 and FANCI decreased, were also decreased after PM2.5 exposure in ATM‐siRNA‐transfected HBE cells. In conclusion, PM2.5‐induced airway inflammation is alleviated in ATM+/− mice compared with WT mice. ATM promotes PM2.5‐induced airway inflammation, which may be attributed to the regulation of DNA damage and DDR.
Funder
National Natural Science Foundation of China
Subject
Health, Toxicology and Mutagenesis,Management, Monitoring, Policy and Law,Toxicology,General Medicine
Cited by
1 articles.
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