Ozone-induced IL-17A and neutrophilic airway inflammation is orchestrated by the caspase-1-IL-1 cascade

被引:36
作者
Che, Luanqing [1 ]
Jin, Yan [1 ,4 ]
Zhang, Chao [1 ]
Lai, Tianwen [1 ]
Zhou, Hongbin [1 ]
Xia, Lixia [1 ]
Tian, Baoping [1 ]
Zhao, Yun [1 ]
Liu, Juan [1 ]
Wu, Yinfang [1 ]
Wu, Yanping [1 ]
Du, Jie [2 ]
Li, Wen [1 ]
Ying, Songmin [1 ]
Chen, Zhihua [1 ]
Shen, Huahao [1 ,3 ]
机构
[1] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Resp & Crit Care Med, Hangzhou 310009, Zhejiang, Peoples R China
[2] Capital Med Univ, Beijing Anzhen Hosp, Key Lab Remodeling Related Cardiovasc Dis, Minist Educ,Beijing Inst Heart Lung & Blood Vesse, Beijing 100029, Peoples R China
[3] State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China
[4] Taizhou Municipal Hosp, Dept Resp Dis, Taizhou 318000, Zhejiang, Peoples R China
来源
SCIENTIFIC REPORTS | 2016年 / 6卷
关键词
INDUCED LUNG INFLAMMATION; GAMMA-DELTA; T-CELLS; INTERLEUKIN-1; RECEPTOR; AIM2; INFLAMMASOME; OXIDATIVE STRESS; INNATE IMMUNITY; SUBACUTE OZONE; AMBIENT OZONE; RESPONSES;
D O I
10.1038/srep18680
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Ozone is a common environmental air pollutant leading to respiratory illness. The mechanisms regulating ozone-induced airway inflammation remain poorly understood. We hypothesize that ozone-triggered inflammasome activation and interleukin (IL)-1 production regulate neutrophilic airway inflammation through IL-17A. Pulmonary neutrophilic inflammation was induced by extended (72 h) low-dose (0.7 ppm) exposure to ozone. IL-1 receptor 1 (Il1r1)(-/-), Il17 alpha(-/-) mice and the caspase-1 inhibitor acetyl-YVAD-chloromethylketone (Ac-YVAD-cmk) were used for in vivo studies. Cellular inflammation and protein levels in bronchial alveolar lavage fluid (BALF), cytokines, and IL-17A-producing gamma delta T-cells, as well as mitochondrial reactive oxygen species (ROS), mitochondrial DNA (mtDNA) release, and inflammasome activation in lung macrophages were analyzed. Ozone-induced neutrophilic airway inflammation, accompanied an increased production of IL-1 beta, IL-18, IL-17A, Granulocyte-colony stimulating factor (G-CSF), Interferon-gamma inducible protein 10 (IP-10) and BALF protein in the lung. Ozone-induced IL-17A production was predominantly in.dT-cells, and Il17 alpha-knockout mice exhibited reduced airway inflammation. Lung macrophages from ozone-exposed mice exhibited higher levels of mitochondrial ROS, enhanced cytosolic mtDNA, increased caspase-1 activation, and higher production of IL-1 beta. Il1r1-knockout mice or treatment with Ac-YVAD-cmk decreased the IL-17A production and subsequent airway inflammation. Taken together, we demonstrate that ozone-induced IL-17A and neutrophilic airway inflammation is orchestrated by the caspase-1-IL-1 cascade.
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页数:11
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