Obesity and airway responsiveness: role of TNFR2.
Obesity and airway responsiveness: role of TNFR2.
复制标题
DOI：
10.1016/j.pupt.2012.05.001
复制
发表时间：
2013-08
影响因子：
3.2
通讯作者：
Shore SA
中科院分区：
文献类型：
--
作者：
Williams AS;Chen L;Kasahara DI;Si H;Wurmbrand AP;Shore SA
肥胖小鼠表现出天生的呼吸道高反应性(AHR)，这是哮喘的一个特征。肿瘤坏死因子α与肥胖和哮喘的疾病进展和慢性炎症状态有关。肿瘤坏死因子通过两种肿瘤坏死因子受体发挥作用，即肿瘤坏死因子受体1和肿瘤坏死因子R2。为了研究TnFR2在肥胖小鼠中观察到的AHR中的作用，我们建立了TnFR2充足或缺乏的肥胖Cpe胖小鼠(分别为CPEFAT和CpeFAT/TnFR2−/−小鼠)，并将它们与它们的瘦对照组(WT和TnFR2−/−小鼠)进行比较。与WT小鼠相比，CPEFAT小鼠对雾化乙酰甲胆碱(用强迫振荡技术测量)表现出AHR，而在CPEFAT/TnFR2−/−小鼠中被消融。BioPlex或EL ISA检测显示肥胖小鼠血清瘦素、G-CSF、IL-7、IL-17A、肿瘤坏死因子α和KC显著升高，与肥胖相关的支气管肺泡灌洗液中G-CSF和IP-10显著升高，与TNFR2状态无关。重要的是，在CPEFAT/TNFR2−/−小鼠中，BALF IL-17A显著高于瘦身对照组，但没有。功能注释聚类从微阵列分析中识别的显著受影响的基因通过比较Cpefat和WT小鼠肺中的基因表达，确定血管形态发生是受肥胖影响最大的基因本体论类别。这一类别包括几个与AHR相关的基因，包括内皮素和TrkB。肥胖使TNFR2充足而不缺乏的小鼠肺组织内皮素和TrkB的mRNA表达增加。我们的结果表明，TNFR2信号是肥胖小鼠先天AHR发育所必需的，并提示TNFR2可能通过促进IL-17A、内皮素和/或TrkB的表达而发挥作用。
Obese mice exhibit innate airway hyperresponsiveness (AHR), a feature of asthma. Tumor necrosis factor alpha (TNFα) is implicated in the disease progression and chronic inflammatory status of both obesity and asthma. TNF acts via two TNF receptors, TNFR1 and TNFR2. To examine the role of TNFR2 in the AHR observed in obese mice, we generated obese Cpefat mice that were either sufficient or deficient in TNFR2 (Cpefat and Cpefat/TNFR2−/− mice, respectively) and compared them with their lean controls (WT and TNFR2−/− mice). Compared to WT mice, Cpefat mice exhibited AHR to aerosolized methacholine (measured using the forced oscillation technique) which was ablated in Cpefat/TNFR2−/− mice. Bioplex or ELISA assay indicated significant increases in serum leptin, G-CSF, IL-7, IL-17A, TNFα, and KC in obese versus lean mice, as well as significant obesity-related increases in bronchoalveolar lavage fluid (BALF) G-CSF and IP-10, regardless of TNFR2 status. Importantly, BALF IL-17A was significantly increased over lean controls in Cpefat but not Cpefat/TNFR2−/− mice. Functional annotation clustering of significantly affected genes identified from microarray analysis comparing gene expression in lungs of Cpefat and WT mice, identified blood vessel morphogenesis as the gene ontology category most affected by obesity. This category included several genes associated with AHR, including endothelin and trkB. Obesity increased pulmonary mRNA expression of endothelin and trkB in TNFR2 sufficient but not deficient mice. Our results indicate that TNFR2 signaling is required for the innate AHR that develops in obese mice, and suggest that TNFR2 may act by promoting IL-17A, endothelin, and/or trkB expression.
登录
查看更多内容
影响因子：
8.3
作者：
Cardillo, C;Campia, U;Panza, JA
通讯作者：
Panza, JA
DOI：
10.1164/rccm.200702-323oc
发表时间：
2007-10-01
影响因子：
24.7
作者：
Johnston, Richard A.;Zhu, Ming;Shore, Stephanie A.
通讯作者：
Shore, Stephanie A.
DOI：
10.1152/ajpregu.00306.2005
发表时间：
2006-01-01
影响因子：
2.8
作者：
Johnston, RA;Theman, TA;Shore, SA
通讯作者：
Shore, SA
DOI：
10.1016/j.jaci.2011.06.009
发表时间：
2011-09
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Dixon AE;Pratley RE;Forgione PM;Kaminsky DA;Whittaker-Leclair LA;Griffes LA;Garudathri J;Raymond D;Poynter ME;Bunn JY;Irvin CG
通讯作者：
Irvin CG
影响因子：
8.9
作者：
Burger, Charles D.;Foreman, Aimee J.;Badesch, David B.
通讯作者：
Badesch, David B.