Allergic asthma accelerates atherosclerosis dependent on Th2 and Th17 in apolipoprotein E deficient mice

被引:37
作者
Wang, Lijun [1 ,3 ]
Gao, Shanshan [1 ]
Xu, Wei [1 ]
Zhao, Sijia [1 ]
Zhou, Juan [1 ,3 ]
Wang, Nanping [4 ]
Yuan, Zuyi [1 ,2 ,3 ,4 ]
机构
[1] Xi An Jiao Tong Univ, Affiliated Hosp 1, Sch Med, Dept Cardiovasc Med, Xian 710061, Shaanxi, Peoples R China
[2] Xi An Jiao Tong Univ, Minist Educ, Key Lab Environm & Genes Related Dis, Xian 710061, Shaanxi, Peoples R China
[3] Key Lab Mol Cardiol, Xian, Shaanxi Provinc, Peoples R China
[4] Xi An Jiao Tong Univ, Cardiovasc Res Ctr, Xian 710061, Shaanxi, Peoples R China
关键词
Allergic asthma; Atherosclerosis; Regulatory T cells; Effector T cells; Apolipoprotein E deficient mice; REGULATORY T-CELLS; CORONARY-HEART-DISEASE; MAST-CELLS; LESION FORMATION; EFFECTOR; RESPONSES; RISK; INTERLEUKIN-4; ATHEROGENESIS; PIOGLITAZONE;
D O I
10.1016/j.yjmcc.2014.02.005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims. The chronic inflammation of atherosclerosis is regulated by Thl, while allergic asthma is controlled by Th2. The direct relationship between atherosclerosis and asthma is contradictory. The aim of this study was to investigate the role of allergic asthma in atherosclerotic plaque formation and the change of CD4(+) T cells subsets. Methods and results. Six-week C57BL/6J or apoE(-)/(-) mice were sensitized on day 0, 7 and 14, then exposed to aerosolized 1% Ovalbumin (OVA) or PBS 30 min/day, 3 times/week for 8 or 16 weeks from day 14 onward. The results showed that allergic asthma mice models were successfully established and the accelerated atherosclerosis induced by allergic asthma accompanied with increased Th2 and Th17 cells but not Thl cells in spleen. Moreover, the expression and production of Th2 and Th17 biomarkers including IL-4 and IL-17A were significantly elevated in asthmatic apoE(-/-) mice. After 8-week treated with the neutralizing antibody of IL-4 or IL-17A, the lesion area in the aortic root of asthmatic apoE(-/-) mice was markedly decreased, and more dramatical result was observed after the combined treatment with IL-4 and IL-17A mAbs. The expression of IgE and Fc epsilon RI alpha in the aortic root of apoE(-/-) mice was markedly increased but was significantly reduced after 8-week treatment with IL-4 mAb. Conclusion. Allergic asthma accelerates atherosclerosis by modulating the balance of Teff/Treg cells in apoE(-/-) mice, which is associated with increased Th2 and Th17 cells but not Th1 cells. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:20 / 27
页数:8
相关论文
共 36 条
[21]   IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines [J].
Molet, S ;
Hamid, Q ;
Davoine, F ;
Nutku, E ;
Taha, R ;
Pagé, N ;
Olivenstein, R ;
Elias, J ;
Chakir, J .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2001, 108 (03) :430-438
[22]   Antigen-specific T cell Sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses [J].
Nakae, S ;
Komiyama, Y ;
Nambu, A ;
Sudo, K ;
Iwase, M ;
Homma, I ;
Sekikawa, K ;
Asano, M ;
Iwakura, Y .
IMMUNITY, 2002, 17 (03) :375-387
[23]   Selective deregulation in chemokine signaling pathways of CD4+CD25hiCD127lo/- regulatory T cells in human allergic asthma [J].
Nguyen, Khoa D. ;
Vanichsarn, Christopher ;
Fohner, Alison ;
Nadeau, Kari C. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2009, 123 (04) :933-939
[24]   Tryptase inhibition blocks airway inflammation in a mouse asthma model [J].
Oh, SW ;
Pae, CI ;
Lee, DK ;
Jones, F ;
Chiang, GKS ;
Kim, HO ;
Moon, SH ;
Cao, BL ;
Ogbu, C ;
Jeong, KW ;
Kozu, G ;
Nakanishi, H ;
Kahn, M ;
Chi, EY ;
Henderson, WR .
JOURNAL OF IMMUNOLOGY, 2002, 168 (04) :1992-2000
[25]   Relation of adult-onset asthma to coronary heart disease and stroke [J].
Onufrak, Stephen J. ;
Abramson, Jerome L. ;
Austin, Harland D. ;
Holguin, Fernando ;
McClellan, William M. ;
Vaccarino, L. Viola .
AMERICAN JOURNAL OF CARDIOLOGY, 2008, 101 (09) :1247-1252
[26]   PREDOMINANT TH2-LIKE BRONCHOALVEOLAR LYMPHOCYTE-T POPULATION IN ATOPIC ASTHMA [J].
ROBINSON, DS ;
HAMID, Q ;
YING, S ;
TSICOPOULOS, A ;
BARKANS, J ;
BENTLEY, AM ;
CORRIGAN, C ;
DURHAM, SR ;
KAY, AB .
NEW ENGLAND JOURNAL OF MEDICINE, 1992, 326 (05) :298-304
[27]   Asthma and incident cardiovascular disease: The Atherosclerosis Risk in Communities Study [J].
Schanen, JG ;
Iribarren, C ;
Shahar, E ;
Punjabi, NM ;
Rich, SS ;
Sorlie, PD ;
Folsom, AR .
THORAX, 2005, 60 (08) :633-638
[28]   Genetically programmed biases in Th1 and Th2 immune responses modulate atherogenesis [J].
Schulte, Stephanie ;
Sukhova, Galina K. ;
Libby, Peter .
AMERICAN JOURNAL OF PATHOLOGY, 2008, 172 (06) :1500-1508
[29]   ACQUISITION OF LYMPHOKINE-PRODUCING PHENOTYPE BY CD4+ T-CELLS [J].
SEDER, RA ;
PAUL, WE .
ANNUAL REVIEW OF IMMUNOLOGY, 1994, 12 :635-673
[30]   Antiatherogenic effect of pioglitazone on uremic apolipoprotein E knockout mice by modulation of the balance of regulatory and effector T cells [J].
Shen, Yan ;
Yuan, Zuyi ;
Yin, Aiping ;
Liu, Yan ;
Xiao, Yan ;
Wu, Yue ;
Wang, Lijun ;
Liang, Xiao ;
Zhao, Yan ;
Tian, Yuling ;
Liu, Weimin ;
Chen, Tao ;
Kishimoto, Chiharu .
ATHEROSCLEROSIS, 2011, 218 (02) :330-338