CARD9-mediated ambient PM2.5-induced pulmonary injury is associated with Th17 cell.
Inflammation and oxidative stress are important risk factors in PM2.5-induced injury. The current study attempted to study the role of caspase recruitment domain (CARD) 9 in ambient PM2.5-induced pulmonary injury in mice. The CARD9-/-and C57BL/6 mice were exposed to 3.6, 7.8 and 15.6mg/kgbw of PM2.5or saline by intratracheal instillation. After the last PM2.5exposure, the spleen, bronchoalveolar lavage fluid (BALF) and pulmonary tissue were collected and examined. The results showed that PM2.5exposure induced inflammatory cell infiltration and alveolar septal thickening in the lung. Regulatory T (Treg) cells in spleen of CARD9-/-mice were significantly higher than that in the C57BL/6 mice, whereas the T helper cells 17 (Th17) were lower. The levels of interleukin (IL)-6 and IL-17A in BALF of the CARD9-/-mice were significantly lower than that in the C57BL/6 mice. The mRNA expression of IL-17A, IL-6 and RORγt in the lung of the CARD9-/-mice is significantly lower than that in the C57BL/6 mice, whereas the mRNA levels of Foxp3 in CARD9-/-mice were significantly higher than that in the C57BL/6 mice at the same dose of PM2.5. The protein expression of nuclear factor κB (NF-κB) is higher in the C57BL/6 mice than that in the CARD9-/-mice. This study indicates that ambient PM2.5-induced pulmonary injury is associated with the immune and inflammatory response. CARD9-mediated Th17/Treg differentiation probably played an important role in PM2.5-induced pulmonary damage.
Department of Environmental Health, School of Public Health and the Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.
Shuo
S
Jiang
Department of Environmental Health, School of Public Health and the Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.
Liang
L
Bo
Department of Environmental Health, School of Public Health and the Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.
Xihao
X
Du
Department of Environmental Health, School of Public Health and the Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.
Jie
J
Liu
Department of Environmental Health, School of Public Health and the Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.
Xuejiao
X
Zeng
University of Wyoming School of Pharmacy, College of Health Sciences, Laramie, WY, USA.
Guanglong
G
He
Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Qinghua
Q
Sun
Department of Environmental Health, School of Public Health and the Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.
Haidong
H
Kan
Department of Environmental Health, School of Public Health and the Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.
Weimin
W
Song
Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, 1665 Kong Jiang Road, Shanghai, 200092 China. Electronic address: xyqah@163.com.
Yuquan
Y
Xie
Department of Environmental Health, School of Public Health and the Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China; Shanghai Key Laboratory of Meteorology and Health, Shanghai, China. Electronic address: jinzhuozhao@fudan.edu.cn.
Jinzhuo
J
Zhao
D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D020381:Interleukin-17 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D055370:Lung Injury / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D000393:Air Pollutants; D053468:CARD Signaling Adaptor Proteins; C513280:Card9 protein, mouse; D020381:Interleukin-17; D015850:Interleukin-6; D052638:Particulate Matter; C577686:interleukin-6, mouse
CARD9; Fine particulate matter; Inflammation; Th17