Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice
Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice
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DOI：
10.1016/j.jaci.2006.04.021
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发表时间：
2006-08-01
影响因子：
14.2
通讯作者：
Hug, Christopher
中科院分区：
文献类型：
--
作者：
Shore, Stephanie A.;Terry, Raya D.;Hug, Christopher
背景：流行病学数据显示肥胖人群哮喘发病率增加。目的：由于肥胖者血清中胰岛素增敏和抗炎性脂肪细胞因子脂联素水平降低，我们试图确定外源性脂联素是否可以减轻过敏性呼吸道反应。在小鼠体内植入阿尔茨海默特微渗泵，持续输注缓冲液或脂联素(1.0mug/g/d)，导致血清脂联素水平增加约60%。2天后，用雾化生理盐水或卵清蛋白激发小鼠，每天1次，连续3天。结果：OVA激发增强了小鼠对静注乙酰甲胆碱、支气管肺泡灌洗液细胞和T(H)2细胞因子水平的反应性。重要的是，与缓冲液相比，脂联素处理的小鼠对OVA的每一种反应都有所减少。OVA攻击导致血清脂联素水平下降30%，脂肪组织脂联素mRNA表达相应下降。OVA攻击还降低了3种脂联素结合蛋白(脂联素受体1、脂联素受体2和T-钙粘素)的mRNA表达。结论：血清脂联素在肺部变态反应中降低，脂联素可减轻小鼠过敏性气道炎症和气道高反应性。
Background: Epidemiologic data indicate an increased incidence of asthma in the obese.Objective: Because serum levels of the insulin-sensitizing and anti-inflammatory adipokine adiponectin are reduced in obese individuals, we sought to determine whether exogenous adiponectin can attenuate allergic airway responses.Methods: We sensitized and challenged BALB/cJ mice with ovalbumin (OVA). Alzet micro-osmotic pumps were implanted in the mice to deliver continuous infusions of buffer or adiponectin (1.0 mu g/g/d), which resulted in an approximate 60% increase in serum adiponectin levels. Two days later, mice were challenged with aerosolized saline or OVA once per day for 3 days. Mice were examined 24 hours after the last challenge.Results: OVA challenge increased airway responsiveness to intravenous methacholine, bronchoalveolar lavage fluid cells, and T(H)2 cytokine levels. Importantly, each of these responses to OVA was reduced in adiponectin- versus buffer-treated mice. OVA challenge caused a 30% reduction in serum adiponectin levels and a corresponding decrease in adipose tissue adiponectin mRNA expression. OVA challenge also decreased pulmonary mRNA expression of each of 3 proposed adiponectin-binding proteins, adiponectin receptor 1, adiponectin receptor 2, and T-cadherin.Conclusion: Our results indicate that serum adiponectin is reduced during pulmonary allergic reactions and that adiponectin attenuates allergic airway inflammation and airway hyperresponsiveness in mice.Clinical implications: The data suggest that adiponectin might play a role in the relationship between obesity and asthma.