Obesity shifts house dust mite-induced airway cellular infiltration from eosinophils to macrophages: effects of glucocorticoid treatment.
Obesity shifts house dust mite-induced airway cellular infiltration from eosinophils to macrophages: effects of glucocorticoid treatment.
复制标题
DOI：
10.1007/s12026-015-8717-2
复制
发表时间：
2015-12
影响因子：
4.4
通讯作者：
Metz CN
中科院分区：
文献类型：
--
作者：
Diaz J;Warren L;Helfner L;Xue X;Chatterjee PK;Gupta M;Solanki MH;Esposito M;Bonagura V;Metz CN
虽然哮喘的典型特征是慢性气道炎症伴嗜酸性粒细胞浸润，但哮喘是一种复杂的多因素疾病，具有多种临床表型。流行病学研究强烈支持肥胖和哮喘之间的联系，并表明肥胖先于并促进哮喘的发展，增加哮喘的严重程度，并降低类固醇的反应性。采用C57BL/6小鼠气道高反应性屋尘螨（HDM）模型，研究饮食性肥胖对变应性气道炎症的影响及地塞米松的治疗作用。与瘦小鼠相比，肥胖-HDM小鼠血浆脂联素（一种抗炎脂肪因子）减少，肺和支气管肺泡灌洗液中嗜酸性粒细胞减少，巨噬细胞浸润增加，肺中巨噬细胞总、M1和M2标记物表达增加，肺中Th2和非Th2细胞因子表达增强。虽然肥胖- hdm小鼠的th2相关反应被全身地塞米松抑制，但几种th2非依赖性反应，包括肺中总和M1巨噬细胞标志物，以及肺CXC-motif配体1 （CXCL1）水平，在地塞米松治疗后没有改善。因此，HDM合并肥胖促进了混合性局部炎症反应（如M1、M2、Th1和Th2），并将细胞浸润从嗜酸性粒细胞转移到巨噬细胞，而巨噬细胞对地塞米松调节不太敏感。由于肥胖哮喘患者表现出更严重的症状，缺乏Th2生物标志物的优势，并且与瘦哮喘患者相比，预计会有更多的类固醇抵抗，因此该模型可用于研究肥胖- hdm小鼠的钝性类固醇反应，并定义肺中发现的巨噬细胞。
Although classically characterized by chronic airway inflammation with eosinophil infiltration, asthma is a complex and multifactorial condition with numerous clinical phenotypes. Epidemiological studies strongly support the link between obesity and asthma and suggest that obesity precedes and promotes asthma development, increases asthma severity, and reduces steroid responsivity. Using a house dust mite (HDM) model of airway hyperresponsiveness in C57BL/6 mice, we examined the effects of diet-induced obesity on allergic airway inflammation and its treatment with dexamethasone. When compared to lean mice treated with HDM, obese-HDM mice had reduced plasma adiponectin, an anti-inflammatory adipokine, lower eosinophil and higher macrophage infiltration into the lungs and bronchoalveolar lavage (BAL) fluid, increased expression of total, M1 and M2 macrophage markers in the lungs, and enhanced Th2 and non-Th2 cytokine expression in the lungs. While Th2-associated responses in obese-HDM mice were suppressed by systemic dexamethasone, several Th2-independent responses, including total and M1 macrophage markers in the lungs, and lung CXC-motif ligand 1 (CXCL1) levels, were not improved following dexamethasone treatment. Thus, HDM combined with obesity promotes mixed localized inflammatory responses (e.g. M1, M2, Th1, and Th2) and shifts the cellular infiltration from eosinophils to macrophages, which are less sensitive to dexamethasone regulation. Because obese asthmatics exhibit more severe symptoms, lack a predominance of Th2 biomarkers and are predicted to experience more steroid resistance when compared to lean asthmatics, this model could be used to study blunted steroid responses in obese-HDM mice and to define the macrophages found in the lungs.
登录
查看更多内容
DOI：
10.1016/j.jaci.2008.07.007
发表时间：
2008-09
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Goleva E;Hauk PJ;Hall CF;Liu AH;Riches DW;Martin RJ;Leung DY
通讯作者：
Leung DY
影响因子：
120.7
作者：
Hedley, AA;Ogden, CL;Flegal, KM
通讯作者：
Flegal, KM
DOI：
10.1164/rccm.200308-1094oc
发表时间：
2004-02-01
影响因子：
24.7
作者：
Johnson, JR;Wiley, RE;Jordana, M
通讯作者：
Jordana, M
DOI：
10.1164/rccm.200507-1046oc
发表时间：
2006-03-15
影响因子：
24.7
作者：
Goleva, E;Li, LB;Leung, DYM
通讯作者：
Leung, DYM
影响因子：
13
作者：
Ahmed, Mushtaq;Gaffen, Sarah L.
通讯作者：
Gaffen, Sarah L.