在长期暴露于环境烟草烟雾和变应原的小鼠中，Toll样受体9激动剂抑制气道炎症、重构和高反应性
2010/02/23
背景：非吸烟者被动接触环境烟草烟雾（ETS）会增加哮喘症状和哮喘恶化。在小鼠模型中，与单独卵清蛋白（OVA）或ETS刺激相比，OVA+ETS显著增加气道嗜酸性细胞炎症和气道重构。本实验旨在研究Toll样受体9（TLR-9）激动剂是否能降低气道炎症、气道重构和气道高反应性（AHR）水平。
方法：将使用或不使用TLR-9激动剂治疗的小鼠采用OVA致敏，并采用OVA＋ETS继发持续1个月。在插管和通气小鼠中评价乙酰甲胆碱使诱导的AHR。采用ELISA检测肺Th2细胞因子和TGFβ1水平。此外，对肺进行组织学处理，采用图像分析定量检测嗜酸性粒细胞、粘液、支气管周围纤维化及平滑肌变化。
结果：TLR-9激动剂用于治疗长期同时暴露于ETS和OVA的小鼠能显著降低气道嗜酸性粒细胞性炎症、粘液分泌、支气管周围纤维化、支气管周围平滑肌层厚度和AHR。TLR-9激动剂治疗小鼠气道重构下降与支气管周围MBP阳性和TGFβ1阳性细胞数明显降低，以及肺Th2细胞因子（IL-5和IL-13）水平和GFβ1表达显著下降相关。
结论：上述结果显示，在暴露于ETS和过敏原，表现为气道炎症和重构增强的小鼠中，基于TLR-9的治疗能明显抑制气道炎症、气道重构和AHR。
（苏楠 审校）
Int Arch Allergy Immunol. 2009 Oct 22;151(4):285-296.
Toll-Like Receptor-9 Agonist Inhibits Airway Inflammation, Remodeling and Hyperreactivity in Mice Exposed to Chronic Environmental Tobacco Smoke and Allergen.
Song DJ, Min MG, Miller M, Cho JY, Yum HY, Broide DH.
Background: As passive environmental tobacco smoke (ETS) exposure in nonsmokers can increase both asthma symptoms and the frequency of asthma exacerbations, we utilized a mouse model, in which ovalbumin (OVA) + ETS induce significantly increased levels of eosinophilic airway inflammation and remodeling compared to either stimulus alone, to determine whether a Toll-like receptor-9 (TLR-9) agonist could reduce levels of airway inflammation, airway remodeling and airway hyperreactivity (AHR). Methods: Mice treated with or without a TLR-9 agonist were sensitized to OVA and challenged with OVA + ETS for 1 month. AHR to methacholine was assessed in intubated and ventilated mice. Lung Th2 cytokines and TGF-beta(1) were measured by ELISA. Lungs were processed for histology and immunohistology to quantify eosinophils, mucus, peribronchial fibrosis and smooth muscle changes using image analysis. Results: Administration of a TLR-9 agonist to mice coexposed to chronic ETS and chronic OVA allergen significantly reduced levels of eosinophilic airway inflammation, mucus production, peribronchial fibrosis, the thickness of the peribronchial smooth muscle layer, and AHR. The reduced airway remodeling in mice treated with the TLR-9 agonist was associated with significantly reduced numbers of peribronchial MBP+ and peribronchial TGF-beta(1)+ cells, and with significantly reduced levels of lung Th2 cytokines [interleukin-5 and interleukin-13] and TGF-beta(1). Conclusion: These studies demonstrate that TLR-9-based therapies inhibit airway inflammation, remodeling and AHR in mice coexposed to ETS and allergen who exhibit enhanced airway inflammation and remodeling.
Int Arch Allergy Immunol. 2009 Oct 22;151(4):285-296.
方法：将使用或不使用TLR-9激动剂治疗的小鼠采用OVA致敏，并采用OVA＋ETS继发持续1个月。在插管和通气小鼠中评价乙酰甲胆碱使诱导的AHR。采用ELISA检测肺Th2细胞因子和TGFβ1水平。此外，对肺进行组织学处理，采用图像分析定量检测嗜酸性粒细胞、粘液、支气管周围纤维化及平滑肌变化。
结果：TLR-9激动剂用于治疗长期同时暴露于ETS和OVA的小鼠能显著降低气道嗜酸性粒细胞性炎症、粘液分泌、支气管周围纤维化、支气管周围平滑肌层厚度和AHR。TLR-9激动剂治疗小鼠气道重构下降与支气管周围MBP阳性和TGFβ1阳性细胞数明显降低，以及肺Th2细胞因子（IL-5和IL-13）水平和GFβ1表达显著下降相关。
结论：上述结果显示，在暴露于ETS和过敏原，表现为气道炎症和重构增强的小鼠中，基于TLR-9的治疗能明显抑制气道炎症、气道重构和AHR。
（苏楠 审校）
Int Arch Allergy Immunol. 2009 Oct 22;151(4):285-296.
Toll-Like Receptor-9 Agonist Inhibits Airway Inflammation, Remodeling and Hyperreactivity in Mice Exposed to Chronic Environmental Tobacco Smoke and Allergen.
Song DJ, Min MG, Miller M, Cho JY, Yum HY, Broide DH.
Background: As passive environmental tobacco smoke (ETS) exposure in nonsmokers can increase both asthma symptoms and the frequency of asthma exacerbations, we utilized a mouse model, in which ovalbumin (OVA) + ETS induce significantly increased levels of eosinophilic airway inflammation and remodeling compared to either stimulus alone, to determine whether a Toll-like receptor-9 (TLR-9) agonist could reduce levels of airway inflammation, airway remodeling and airway hyperreactivity (AHR). Methods: Mice treated with or without a TLR-9 agonist were sensitized to OVA and challenged with OVA + ETS for 1 month. AHR to methacholine was assessed in intubated and ventilated mice. Lung Th2 cytokines and TGF-beta(1) were measured by ELISA. Lungs were processed for histology and immunohistology to quantify eosinophils, mucus, peribronchial fibrosis and smooth muscle changes using image analysis. Results: Administration of a TLR-9 agonist to mice coexposed to chronic ETS and chronic OVA allergen significantly reduced levels of eosinophilic airway inflammation, mucus production, peribronchial fibrosis, the thickness of the peribronchial smooth muscle layer, and AHR. The reduced airway remodeling in mice treated with the TLR-9 agonist was associated with significantly reduced numbers of peribronchial MBP+ and peribronchial TGF-beta(1)+ cells, and with significantly reduced levels of lung Th2 cytokines [interleukin-5 and interleukin-13] and TGF-beta(1). Conclusion: These studies demonstrate that TLR-9-based therapies inhibit airway inflammation, remodeling and AHR in mice coexposed to ETS and allergen who exhibit enhanced airway inflammation and remodeling.
Int Arch Allergy Immunol. 2009 Oct 22;151(4):285-296.
