5A,一种载脂蛋白A-I模拟肽, 能抑制屋尘螨诱导的哮喘
2011/03/28
摘要
有必要开发新的哮喘治疗措施。载脂蛋白A-I (apoA-I)是高密度脂蛋白的主要组成，介导了胆固醇的反向转运，具有动脉保护和抗炎作用。本研究中，我们假设apoA-I 模拟肽能有效抑制哮喘患者的气道炎症。5A肽为一合成的双螺旋apoA-I模拟肽，在屋尘螨(HDM)诱导哮喘前，通过微型渗透泵将5A注入野生型A/J 小鼠体内。
我们结果显示，在注射5A apoA-I模拟肽后，HDM诱导的哮喘小鼠，其支气管肺泡灌洗液中嗜酸性粒细胞、淋巴细胞和中性粒细胞数显著减少，组织学显示气道炎症显著改善。气道炎症的缓解与Th1和Th17型细胞因子表达下降及促进T细胞和嗜酸性粒细胞趋化的趋化因子（包括CCL7, CCL17, CCL11和CCL24）表达下降有关。此外，5A apoA-I模拟肽能抑制HDM诱导哮喘小鼠肺内巨噬细胞的活化，降低气道高反应性的发展和抑制气道重构（包括杯状细胞过度增生和胶原蛋白[Col1a1和Col3a1]过度表达）。
我们结果显示，5A apoA-I模拟肽能缓解HDM诱导的小鼠哮喘模型中气道炎症的进展和气道高反应性。这些结果表明，apoA-I模拟肽（如5A）可以开发作为一种哮喘的治疗新方法。
（苏楠 审校）
J Immunol. 2011 Jan 1;186(1):576-583.
5A, an Apolipoprotein A-I Mimetic Peptide, Attenuates the Induction of House Dust Mite-Induced Asthma.
Yao X, Dai C, Fredriksson K, Dagur PK, McCoy JP, Qu X, Yu ZX, Keeran KJ, Zywicke GJ, Amar MJ, Remaley AT, Levine SJ.
Pulmonary and Vascular Medicine Branch.
Abstract
New treatment approaches are needed for patients with asthma. Apolipoprotein A-I (apoA-I), the major structural protein of high-density lipoproteins, mediates reverse cholesterol transport and has atheroprotective and anti-inflammatory effects. In this study, we hypothesized that an apoA-I mimetic peptide might be effective at inhibiting asthmatic airway inflammation. A 5A peptide, which is a synthetic, bihelical apoA-I mimetic, was administered to wild-type A/J mice via osmotic mini-pump prior to the induction of house dust mite (HDM)-induced asthma. HDM-challenged mice that received the 5A apoA-I mimetic peptide had significant reductions in the number of bronchoalveolar lavage fluid eosinophils, lymphocytes, and neutrophils, as well as in histopathological evidence of airway inflammation. The reduction in airway inflammation was mediated by a reduction in the expression of Th2- and Th17-type cytokines, as well as in chemokines that promote T cell and eosinophil chemotaxis, including CCL7, CCL17, CCL11, and CCL24. Furthermore, the 5A apoA-I mimetic peptide inhibited the alternative activation of pulmonary macrophages in the lungs of HDM-challenged mice. It also abrogated the development of airway hyperresponsiveness and reduced several key features of airway remodeling, including goblet cell hyperplasia and the expression of collagen genes (Col1a1 and Col3a1). Our results demonstrate that the 5A apoA-I mimetic peptide attenuates the development of airway inflammation and airway hyperresponsiveness in an experimental murine model of HDM-induced asthma. These data support the conclusion that strategies using apoA-I mimetic peptides, such as 5A, might be developed further as a possible new treatment approach for asthma.
J Immunol. 2011 Jan 1;186(1):576-83..
有必要开发新的哮喘治疗措施。载脂蛋白A-I (apoA-I)是高密度脂蛋白的主要组成，介导了胆固醇的反向转运，具有动脉保护和抗炎作用。本研究中，我们假设apoA-I 模拟肽能有效抑制哮喘患者的气道炎症。5A肽为一合成的双螺旋apoA-I模拟肽，在屋尘螨(HDM)诱导哮喘前，通过微型渗透泵将5A注入野生型A/J 小鼠体内。
我们结果显示，在注射5A apoA-I模拟肽后，HDM诱导的哮喘小鼠，其支气管肺泡灌洗液中嗜酸性粒细胞、淋巴细胞和中性粒细胞数显著减少，组织学显示气道炎症显著改善。气道炎症的缓解与Th1和Th17型细胞因子表达下降及促进T细胞和嗜酸性粒细胞趋化的趋化因子（包括CCL7, CCL17, CCL11和CCL24）表达下降有关。此外，5A apoA-I模拟肽能抑制HDM诱导哮喘小鼠肺内巨噬细胞的活化，降低气道高反应性的发展和抑制气道重构（包括杯状细胞过度增生和胶原蛋白[Col1a1和Col3a1]过度表达）。
我们结果显示，5A apoA-I模拟肽能缓解HDM诱导的小鼠哮喘模型中气道炎症的进展和气道高反应性。这些结果表明，apoA-I模拟肽（如5A）可以开发作为一种哮喘的治疗新方法。
（苏楠 审校）
J Immunol. 2011 Jan 1;186(1):576-583.
5A, an Apolipoprotein A-I Mimetic Peptide, Attenuates the Induction of House Dust Mite-Induced Asthma.
Yao X, Dai C, Fredriksson K, Dagur PK, McCoy JP, Qu X, Yu ZX, Keeran KJ, Zywicke GJ, Amar MJ, Remaley AT, Levine SJ.
Pulmonary and Vascular Medicine Branch.
Abstract
New treatment approaches are needed for patients with asthma. Apolipoprotein A-I (apoA-I), the major structural protein of high-density lipoproteins, mediates reverse cholesterol transport and has atheroprotective and anti-inflammatory effects. In this study, we hypothesized that an apoA-I mimetic peptide might be effective at inhibiting asthmatic airway inflammation. A 5A peptide, which is a synthetic, bihelical apoA-I mimetic, was administered to wild-type A/J mice via osmotic mini-pump prior to the induction of house dust mite (HDM)-induced asthma. HDM-challenged mice that received the 5A apoA-I mimetic peptide had significant reductions in the number of bronchoalveolar lavage fluid eosinophils, lymphocytes, and neutrophils, as well as in histopathological evidence of airway inflammation. The reduction in airway inflammation was mediated by a reduction in the expression of Th2- and Th17-type cytokines, as well as in chemokines that promote T cell and eosinophil chemotaxis, including CCL7, CCL17, CCL11, and CCL24. Furthermore, the 5A apoA-I mimetic peptide inhibited the alternative activation of pulmonary macrophages in the lungs of HDM-challenged mice. It also abrogated the development of airway hyperresponsiveness and reduced several key features of airway remodeling, including goblet cell hyperplasia and the expression of collagen genes (Col1a1 and Col3a1). Our results demonstrate that the 5A apoA-I mimetic peptide attenuates the development of airway inflammation and airway hyperresponsiveness in an experimental murine model of HDM-induced asthma. These data support the conclusion that strategies using apoA-I mimetic peptides, such as 5A, might be developed further as a possible new treatment approach for asthma.
J Immunol. 2011 Jan 1;186(1):576-83..
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Churg-Strauss综合征患者的哮喘病程
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