Jain Vipul V, Kitagaki Kunihiko, Businga Thomas, Hussain Iftikhar, George Caroline, O'shaughnessy Patrick, Kline Joel N
Department of Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, USA.
J Allergy Clin Immunol. 2002 Dec;110(6):867-72. doi: 10.1067/mai.2002.129371.
We have previously demonstrated that CpG oligodeoxynucleotides (CpG-ODNs) protect against eosinophilia and airway hyperresponsiveness in murine 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.
The purpose of this study was to evaluate the effect of CpG-ODNs on chronic inflammatory changes and airway remodeling by using a murine model of chronic allergen-induced asthma.
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.
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 beta, suggesting that regulatory T cells might be responsible for some of these protective effects.
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.
我们之前已经证明，在变应原诱导的哮喘小鼠模型中，CpG寡脱氧核苷酸（CpG-ODN）可预防嗜酸性粒细胞增多和气道高反应性。据推测，急性炎症会诱发慢性气道反应，但之前尚无研究评估CpG-ODN对变应原诱导的气道重塑的影响。由于气道重塑被认为是导致哮喘患者许多长期不良影响的原因，因此我们使用反复暴露于变应原的小鼠模型评估了CpG-ODN是否同样可以预防这些变化。
本研究旨在通过使用慢性变应原诱导的哮喘小鼠模型，评估CpG-ODN对慢性炎症变化和气道重塑的影响。
将C57BL/6小鼠用卵清蛋白（OVA）致敏，随后每周通过吸入雾化OVA 3次，持续6周。一些小鼠在致敏时通过腹腔注射接受CpG-ODN。在暴露期结束时评估小鼠气道炎症、气道高反应性和气道重塑的发展情况。
反复接受OVA气道激发的OVA致敏小鼠出现慢性炎症、持续的气道高反应性以及气道重塑的证据，包括上皮下胶原沉积和杯状细胞增生-化生。在用CpG-ODN治疗的小鼠中，这些变化显著减少。有趣的是，用CpG-ODN治疗的小鼠支气管肺泡灌洗转化生长因子β水平升高，这表明调节性T细胞可能是其中一些保护作用的原因。
CpG-ODN不仅能有效预防急性炎症，而且似乎还能减少慢性变应原暴露后出现的气道重塑标志物。
