CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma
CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma
复制标题
DOI：
10.1067/mai.2002.129371
复制
发表时间：
2002-12-01
影响因子：
14.2
通讯作者：
Kline, JN
中科院分区：
文献类型：
--
作者：
Jain, VV;Kitagaki, K;Kline, JN
背景资料：我们以前已经证明，CpG寡脱氧核苷酸（CpG-ODNs）对嗜酸性粒细胞增多症和过敏原诱导的哮喘的海洋模型气道高反应性的保护。急性炎症被假设为诱导慢性气道反应，但没有以前的研究评估CpG-ODNs对过敏原诱导的气道重塑的影响。由于重塑被认为是哮喘患者长期不良反应的原因，我们评估了CpG-ODNs是否可以使用反复过敏原暴露的小鼠模型类似地预防这些变化。目的：本研究的目的是通过使用慢性过敏原诱导的哮喘的海洋模型来评估CpG-ODNs对慢性炎症变化和气道重塑的影响。方法：使C57 BL/6小鼠对卵清蛋白（OVA）致敏，随后通过每周吸入3次暴露于雾化的OVA，持续6周。一些小鼠在致敏时通过腹腔注射的方式接受CpG-ODNs。在暴露期结束时，小鼠的气道炎症，气道高反应性，和气道remodels.Results的发展进行了评估：OVA致敏小鼠暴露于反复气道挑战与OVA有慢性炎症，持续气道高反应性，和气道重塑的证据，包括上皮下胶原沉积和杯状细胞增生-化生。这些变化在用CpG-ODN处理的小鼠中显著降低。有趣的是，用CpG-ODNs治疗的小鼠表现出支气管肺泡灌洗液转化生长因子P水平的增加，这表明调节性T细胞可能是负责一些这些保护作用。结论：CpG-ODNs是有效的，不仅在预防急性炎症，但也出现减少标记物的气道重塑后，慢性过敏原暴露。
Background: We have previously demonstrated that CpG oligodeoxymicleotides (CpG-ODNs) protect against eosinophilia and airway hyperresponsiveness in marine models of allergen-induced asthma. Acute inflammation is hypothesized to induce chronic airway responses, but no previous studies have evaluated the effects of CpG-ODNs on allergen-induced airway remodeling. Because remodeling is thought to be responsible for many of the long-term adverse effects on asthmatic patients, we evaluated whether CpG-ODNs might similarly prevent these changes using a murine model of recurrent allergen exposure.Objective: The purpose of this study was to evaluate the effect of CpG-ODNs on chronic inflammatory changes and airway remodeling by using a marine model of chronic allergen-induced asthma.Methods: C57BL/6 mice were sensitized to ovalbumin (OVA) and subsequently exposed to nebulized OVA by means of inhalation 3 times weekly for 6 weeks. Some mice received CpG-ODNs by means of intraperitoneal injection at the time of sensitization. At the end of the exposure period, mice were evaluated for the development of airway inflammation, airway hyperresponsiveness, and airway remodeling.Results: OVA-sensitized mice exposed to recurrent airway challenge with OVA have chronic inflammation, persistent airway hyperresponsiveness, and evidence of airway remodeling, including subepithelial collagen deposition and goblet cell hyperplasia-metaplasia. These changes are significantly reduced in mice treated with CpG-ODNs. Interestingly, mice treated with CpG-ODNs exhibit increased levels of bronchoalveolar lavage transforming growth factor P, suggesting that regulatory T cells might be responsible for some of these protective effects.Conclusion: CpG-ODNs are effective not only in preventing acute inflammation but also appear to reduce markers of airway remodeling that develop after chronic allergen exposure.