Long-Term Exposure of Chemokine CXCL10 Causes Bronchiolitis-like Inflammation
Long-Term Exposure of Chemokine CXCL10 Causes Bronchiolitis-like Inflammation
复制标题
DOI：
10.1165/rcmb.2011-0116oc
复制
发表时间：
2012-05-01
影响因子：
6.4
通讯作者：
Noble, Paul W.
中科院分区：
文献类型：
--
作者：
Jiang, Dianhua;Liang, Jiurong;Noble, Paul W.
趋化因子和趋化因子受体与毛细支气管炎的发病机制有关。CXCR 3配体（CXCL 10、CXCL 9和CXCL 11）在闭塞性细支气管炎综合征（BOS）和慢性同种异体排斥反应患者中升高。研究还表明，CXCR 3或其配体的阻断改变了T细胞募集和气道闭塞的结果。我们想确定趋化因子CXCL 10在毛细支气管炎和BOS发病机制中的作用。在本研究中，我们发现BOS患者中CXCL 10 mRNA水平显著升高。我们产生的转基因小鼠表达的小鼠CXCL 10 cDNA的控制下，大鼠CC 10启动子。6个月大的CC 10-CXCL 10转基因小鼠出现毛细支气管炎，其特征为气道上皮增生，并出现细支气管周围和血管周围淋巴细胞浸润。气道增生和T细胞炎症取决于CXCR 3的存在。因此，趋化因子CXCL 10在肺中的长期暴露导致小鼠细支气管炎样炎症。
Chemokines and chemokine receptors have been implicated in the pathogenesis of bronchiolitis. CXCR3 ligands (CXCL10, CXCL9, and CXCL11) were elevated in patients with bronchiolitis obliterans syndrome (BOS) and chronic allorejection. Studies also suggested that blockage of CXCR3 or its ligands changed the outcome of T-cell recruitment and airway obliteration. We wanted to determine the role of the chemokine CXCL10 in the pathogenesis of bronchiolitis and BOS. In this study, we found that CXCL10 mRNA levels were significantly increased in patients with BOS. We generated transgenic mice expressing a mouse CXCL10 cDNA under control of the rat CC10 promoter. Six-month-old CC10-CXCL10 transgenic mice developed bronchiolitis characterized by airway epithelial hyperplasia and developed peribronchiolar and perivascular lymphocyte infiltration. The airway hyperplasia and T-cell inflammation were dependent on the presence of CXCR3. Therefore, long-term exposure of the chemokine CXCL10 in the lung causes bronchiolitis-like inflammation in mice.