Effects of PM2.5 exposure on the Notch signaling pathway and immune imbalance in chronic obstructive pulmonary disease

被引:85
|
作者
Gu, Xing-yu [1 ]
Chu, Xu [1 ]
Zeng, Xiao-Li [1 ]
Bao, Hai-Rong [1 ]
Liu, Xiao-Ju [1 ]
机构
[1] Lanzhou Univ, Hosp 1, Dept Gerontal Resp Med, 1 Dong Gang West Rd, Lanzhou 730000, Peoples R China
基金
中国国家自然科学基金;
关键词
Pulmonary disease; Chronic obstructive; PM2.5; T lymphocytes subset; Notch signaling; Adaptive immunity; PARTICULATE AIR-POLLUTION; REGULATORY T-CELLS; INFLAMMATORY RESPONSES; AMBIENT PM2.5; TH17; ASSOCIATION; INVOLVEMENT; EXPRESSION; INNATE; MATTER;
D O I
10.1016/j.envpol.2017.03.070
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Chronic Obstructive Pulmonary Disease (COPD) is associated with T lymphocytes subset (Th1/Th2, Th17/Treg) imbalance. Notch signaling pathway plays a key role in the development of the adaptive immunity. The immune disorder induced by fine particulate matter (PM2.5) is related to COPD. The aim of this study was to investigate the mechanism by which PM2.5 influences the Notch signaling pathway leading to worsening immune disorder and accelerating COPD development. A COPD mouse model was established by cigarette smoke exposure. PM2.5 exposure was performed by aerosol inhalation. gamma-secretase inhibitor (GSI) was given using intraperitoneal injection. Splenic T lymphocytes were purified using a density gradient centrifugation method. CD4(+) T lymphocyte subsets (Th1/Th2, Th17/Treg) were detected using flow cytometry. mRNA and proteins of Notch1/2/3/4, Hes1/5, and Heyl were detected using RT-PCR and Western blot. Serum INF-gamma, IL-17 and IL-10 concentrations were measured using ELISA. The results showed that in COPD mice Th1% and Th17%, Th1/Th2 and Th17/Treg were increased, and the levels of mRNA and protein in Notch1/2/3/4, Hes1/5, and Heyl and serum INF-gamma and IL-17 concentrations were significantly increased, and Th2%, Treg%, and serum IL-4 and IL-10 concentrations were significantly decreased. COPD Mice have Th1- and Th17-mediated immune disorder, and the Notch signaling pathway is in an overactivated state. PM2.5 promotes the overactivation of the Notch signaling pathway and aggravates the immune disorder of COPD. GSI can partially inhibit the activation of the Notch signaling pathway and alleviate the immune disorder under basal state and the immune disorder of COPD caused by PM2.5. This result suggests that PM2.5 is involved in the immune disorder of mice with COPD by affecting the Notch signaling pathway and that PM2.5 aggravates COPD. (C) 2017 Published by Elsevier Ltd.
引用
收藏
页码:163 / 173
页数:11
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