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过敏性支气管哮喘小鼠气道中ADAM8的上调

Upregulation of ADAM8 in the airways of mice with allergic bronchial asthma.

作者信息

Chiba Yoshihiko, Onoda Satoshi, Hattori Yoshiyuki, Maitani Yoshie, Sakai Hiroyasu, Misawa Miwa

机构信息

Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, Japan.

出版信息

Lung. 2009 May-Jun;187(3):179-85. doi: 10.1007/s00408-009-9145-7. Epub 2009 Apr 17.

Abstract

Recent microarray analyses revealed that a disintegrin and metalloproteinase (ADAM) 8 (ADAM8; also called CD156) is one of the asthma candidate genes. However, the function of ADAM8 and its localization in the airways are still poorly understood. In the present study, the changes in the expression and localization of ADAM8 in the airways of a mouse model of allergic bronchial asthma were investigated. Male BALB/c mice were sensitized and repeatedly challenged with ovalbumin antigen to induce asthmatic response. After the final antigen challenge, mRNA and protein expressions of ADAM8 were elucidated by quantitative RT-PCR and immunohistochemistry. The mRNA expression of ADAM8 in the airways was significantly increased in this animal model of asthma compared with naive animals. Immunohistochemical examinations revealed that ADAM8 was located in airway epithelia, airway smooth muscles, and infiltrated cells (mainly macrophages) into lung parenchyma. A distinctly stronger immunostaining of ADAM8 was observed in these airway cells of the repeatedly antigen-challenged mice compared with those of the sensitized control animals. An upregulation of ADAM8 in the airways might be involved in the pathogenesis of airway inflammation and/or hyperresponsiveness, characteristic features of allergic bronchial asthma.

摘要

最近的微阵列分析显示,去整合素和金属蛋白酶(ADAM)8(ADAM8;也称为CD156)是哮喘候选基因之一。然而,ADAM8的功能及其在气道中的定位仍知之甚少。在本研究中,我们调查了过敏性支气管哮喘小鼠模型气道中ADAM8表达和定位的变化。雄性BALB/c小鼠用卵清蛋白抗原致敏并反复激发以诱导哮喘反应。在最后一次抗原激发后,通过定量RT-PCR和免疫组织化学方法阐明ADAM8的mRNA和蛋白表达。与未处理的动物相比,在该哮喘动物模型中,气道中ADAM8的mRNA表达显著增加。免疫组织化学检查显示,ADAM8位于气道上皮、气道平滑肌以及浸润到肺实质的细胞(主要是巨噬细胞)中。与致敏对照动物相比,在反复接受抗原激发的小鼠的这些气道细胞中观察到ADAM8有明显更强的免疫染色。气道中ADAM8的上调可能参与气道炎症和/或高反应性的发病机制,而气道炎症和高反应性是过敏性支气管哮喘的特征性表现。

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