D-4F, an apoA-1 mimetic, decreases airway hyperresponsiveness, inflammation, and oxidative stress in a murine model of asthma
D-4F, an apoA-1 mimetic, decreases airway hyperresponsiveness, inflammation, and oxidative stress in a murine model of asthma
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DOI：
10.1194/jlr.m012724
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发表时间：
2011-03-01
影响因子：
6.5
通讯作者：
Pritchard, K. A., Jr.
中科院分区：
文献类型：
--
作者：
Nandedkar, S. D.;Weihrauch, D.;Pritchard, K. A., Jr.
哮喘的特点是氧化应激和气道炎症。虽然促炎脂质参与哮喘，但仍然缺乏针对它们的治疗。Ac-DWFKAFYDKVAEKFKEAFNH（2）（4F）是一种载脂蛋白（apo）A-I模拟物，已显示优先结合氧化脂质并改善HDL功能。本研究的目的是确定4F对已建立的哮喘小鼠模型中氧化应激、炎症和气道阻力的影响。我们在这里表明，卵清蛋白（OVA）致敏增加气道高反应性，嗜酸性粒细胞的招聘，并在C57 BL/6J小鼠肺胶原沉积的机制，可以减少4F。OVA致敏诱导了OVA致敏小鼠肺中转化生长因子（TGF）β-1、成纤维细胞特异性蛋白（FSP）-1、抗T15自身抗体染色的显著增加，以及4-羟基壬烯醛（4-HNE）迈克尔加合物的适度增加。4F降低了OVA致敏小鼠肺中的TGF β-1，FSP-1，抗T15自身抗体和4-HNE加合物。支气管肺泡灌洗液（BALF）中的嗜酸性粒细胞过氧化物酶（EPO）活性、外周嗜酸性粒细胞计数、总IgE和促炎性HDL（p-HDL）均在OVA致敏小鼠中升高。4F降低了这些小鼠中的BALF EPO活性、嗜酸性粒细胞计数、总IgE和p-HDL。这些数据表明，4F通过降低氧化应激降低了哮喘实验鼠模型中的肺部炎症和气道阻力。Nandedkar，S. D、D. Weihrauch，H. Xu，Y.施，T. Feroah，W. Hutchins，D. a. Rickaby，N.迪兹居内斯角a. Hillery，K. S. Konduri和K. a.小普里查德D-4F，一种apoA-1模拟物，降低哮喘小鼠模型的气道高反应性、炎症和氧化应激。J. Lipid Res. 2011. 52：499 - 508。
Asthma is characterized by oxidative stress and inflammation of the airways. Although proinflammatory lipids are involved in asthma, therapies targeting them remain lacking. Ac-DWFKAFYDKVAEKFKEAFNH(2) (4F) is an apolipoprotein (apo)A-I mimetic that has been shown to preferentially bind oxidized lipids and improve HDL function. The objective of the present study was to determine the effects of 4F on oxidative stress, inflammation, and airway resistance in an established murine model of asthma. We show here that ovalbumin (OVA)-sensitization increased airway hyperresponsiveness, eosinophil recruitment, and collagen deposition in lungs of C57BL/6J mice by a mechanism that could be reduced by 4F. OVA sensitization induced marked increases in transforming growth factor (TGF)beta-1, fibroblast specific protein (FSP)-1, anti-T15 autoantibody staining, and modest increases in 4-hydroxynonenal (4-HNE) Michael's adducts in lungs of OVA-sensitized mice. 4F decreased TGF beta-1, FSP-1, anti-T15 autoantibody, and 4-HNE adducts in the lungs of the OVA-sensitized mice. Eosinophil peroxidase (EPO) activity in bronchial alveolar lavage fluid (BALF), peripheral eosinophil counts, total IgE, and proinflammatory HDL (p-HDL) were all increased in OVA-sensitized mice. 4F decreased BALF EPO activity, eosinophil counts, total IgE, and p-HDL in these mice.jlr These data indicate that 4F reduces pulmonary inflammation and airway resistance in an experimental murine model of asthma by decreasing oxidative stress.-Nandedkar, S. D., D. Weihrauch, H. Xu, Y. Shi, T. Feroah, W. Hutchins, D. A. Rickaby, N. Duzgunes, C. A. Hillery, K. S. Konduri, and K. A. Pritchard, Jr. D-4F, an apoA-1 mimetic, decreases airway hyperresponsiveness, inflammation, and oxidative stress in a murine model of asthma. J. Lipid Res. 2011. 52: 499-508.