Deficiency of tenascin C attenuates allergen-induced bronchial asthma in the mouse
Deficiency of tenascin C attenuates allergen-induced bronchial asthma in the mouse
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DOI：
10.1002/eji.200636271
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发表时间：
2006-12-01
影响因子：
5.4
通讯作者：
Taguchi, Osamu
中科院分区：
文献类型：
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作者：
Nakahara, Hiroki;Gabazza, Esteban C.;Taguchi, Osamu
Tenascin C （TN-C）是一种细胞外基质糖蛋白，在包括支气管哮喘在内的几种肺部炎症性疾病中表达升高。然而，TN-C在肺部炎症发病机制中的确切功能尚不清楚。在本研究中，我们比较了野生型和tn - c缺陷（-/-）BALB/c小鼠支气管哮喘的程度。用卵清蛋白致敏和攻毒诱导支气管哮喘。用生理盐水处理的同窝鼠作为对照。采用酶免疫法测定支气管肺泡灌洗液和血浆中的细胞因子。与tn - c基因敲除小鼠相比，野生型小鼠肺嗜酸性粒细胞数量显著增加。与野生型小鼠相比，卵清蛋白致敏/攻毒的n- c敲除小鼠气道高反应性、nf - κ B活化和支气管肺泡灌洗液中单核细胞化学引诱蛋白-1、IL-5、IL-13、金属蛋白酶-9和免疫球蛋白- e的浓度显著降低。体外实验表明，TN-C显著刺激脾淋巴细胞分泌IL-5、IL-13、ifn - γ和免疫球蛋白e。这些观察结果提示TN-C参与支气管哮喘的发病机制。
Tenascin C (TN-C) is an extracellular matrix glycoprotein whose expression is increased in several inflammatory diseases of the lung, including bronchial asthma. However, the exact function of TN-C in the pathogenesis of lung inflammation remains unclear. In the present study, we compared the degree of bronchial asthma in wild-type and TN-C-deficient (-/-) BALB/c mice. Bronchial asthma was induced by sensitization and challenge with ovalbumin. Littermates treated with saline were used as controls. Cytokines in bronchoalveolar lavage fluid and plasma were measured by enzyme immunoassays. The number of eosinophils in the lung was significantly increased in wild-type mice compared with TN-C-knockout mice. Airway hyperreactivity, NF-kappa B activation and concentrations of monocyte chemoattractant protein-1, IL-5, IL-13, metalloproteinase-9 and immunoglobulin-E in the bronchoalveolar lavage fluid were significantly decreased in ovalbumin-sensitized/challenged TN-C-knockout mice compared with their wild-rype counterparts. In vitro experiments disclosed that TN-C significantly stimulates the secretion of IL-5, IL-13, IFN-gamma and immunoglobulin-E from spleen lymphocytes. These observations suggest that TN-C is involved in the pathogenesis of bronchial asthma.