Jie Zhijun, Jin Meiling, Cai Yingyun, Bai Chunxue, Shen Yao, Yuan Zhenghong, Hu Yunwen, Holgate Stephen
Department of Respiratory Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Respir Physiol Neurobiol. 2009 Sep 30;168(3):289-94. doi: 10.1016/j.resp.2009.07.019. Epub 2009 Jul 25.
A disintegrin and metalloprotease domain 33 (ADAM33) has been identified as an asthma susceptibility gene, which is associated with small-airway remodeling. However, the role of ADAM33 in the development of allergic airway inflammation is unclear. The present study used an established murine model of allergen-induced chronic airway inflammation, which was sensitized and then challenged by nebulized 2.5% ovalbumin (OVA) for 8 weeks (30 min/day, three times a week). The expression of ADAM33 mRNA detected by real time RT-PCR was significantly enhanced in the lung tissue of mice with OVA challenge, as compared with the group challenged with saline. This OVA-challenged model showed significant Th2-biased airway inflammation as well as airway remodeling with features of sub-epithelial fibrosis and mucus hyper-secretion. Furthermore, in vitro studies showed that IL-4 and IL-13 could significantly up-regulate the expression of ADAM33 mRNA in human fibroblasts in a concentration- and time-dependent manner as compared to normal controls. These results support the note that Th2 cytokines can up-regulate the expression of ADAM33 mRNA and ADAM33 may play an important role in the development of airway remodeling in allergen-induced chronic airway inflammation.
解整合素金属蛋白酶33（ADAM33）已被确定为一种哮喘易感基因，与小气道重塑有关。然而，ADAM33在过敏性气道炎症发展中的作用尚不清楚。本研究使用了一种已建立的变应原诱导的慢性气道炎症小鼠模型，该模型先致敏，然后用雾化的2.5%卵清蛋白（OVA）激发8周（每天30分钟，每周3次）。与盐水激发组相比，通过实时RT-PCR检测到的ADAM33 mRNA在OVA激发的小鼠肺组织中的表达显著增强。该OVA激发模型显示出明显的Th2偏向性气道炎症以及具有上皮下纤维化和黏液高分泌特征的气道重塑。此外，体外研究表明，与正常对照相比，IL-4和IL-13可浓度和时间依赖性地显著上调人成纤维细胞中ADAM33 mRNA的表达。这些结果支持Th2细胞因子可上调ADAM33 mRNA表达且ADAM33可能在变应原诱导的慢性气道炎症气道重塑发展中起重要作用的观点。
