Clarification of the underlying mechanism of allergic diseases targeting the signal pathways of the involved cytokines

阐明针对相关细胞因子信号通路的过敏性疾病的潜在机制

• 批准号: 18604007
• 负责人: IZUHARA Kenji
• 金额: $ 2.69万
• 依托单位: Saga University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18604007/
• 关键词: Allergv; Asthma; Gene; Protein; Immunology

We found in this study that periostin, an extracellular matrix protein, is a component of fibrosis in bronchial asthma and that pendrin, an anion exchanger, is a mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease (COPD). In the former project, we obtained the following results. (1) Upon stimulation of IL-4/IL-13, lung fibroblasts secreted periostin. (2) Periostin was deposited in the fibrotic legions of asthma. (3) Periostin bound to other matrix proteins such as tenascin-C, fibronectin, and collagen V. These results suggest that periostin is secreted from lung fibroblasts stimulated with IL-4/IL-13 in bronchial asthma and is involved in fibrosis of asthma by binding to other matrix proteins. In the latter project, we obtained the following results. (1) Bronchial epithelial cells cultured by the air-interface method in the presence of IL-13 differentiated into mucus-producing cells and these cell expressed pendrin. (2) Expression of pendrin was up-regulated in lung tissues of bronchial asthma and COPD. (3) Enforced expression of pendrin in airway cells caused mucus production. (4) Enforced expression of pendrin into mouse lungs caused mucus production with infiltration of neutrophils. These results suggest that pendrin is induced in the lung tissues of bronchial asthma and COPD and is involved in mucus production in these diseases. Fibrosis and mucus production are deeply correlated with morbidity and mortality of bronchial asthma and COPD. Therefore, the present results are useful to comprehend the whole molecular mechanism of fibrosis and mucus production in bronchial asthma and COPD and to develop therapeutic reagents against these phenotypes.

我们在这项研究中发现，细胞外基质蛋白Periostin是支气管哮喘纤维化的一个组成部分，而阴离子交换器Pendrin是支气管哮喘和慢性阻塞性肺疾病(COPD)粘液产生的媒介。在前一个项目中，我们取得了以下成果。(1)肺成纤维细胞在IL-4/IL-13刺激下分泌Periostin。(2)Periostin在哮喘纤维化军团中沉积。(3)Periostin与其他基质蛋白如Tenascin-C、FN、V型胶原结合。这些结果表明，Periostin是由IL-4/IL-13刺激的哮喘肺成纤维细胞分泌的，并通过与其他基质蛋白结合而参与哮喘的纤维化。在后一个项目中，我们取得了以下成果。(1)在IL-13存在下，空气界面法培养的支气管上皮细胞分化为粘液分泌细胞，并表达侧膜蛋白。(2)支链蛋白在哮喘和COPD肺组织中的表达上调。(3)气道上皮细胞膜蛋白表达增强，导致黏液产生。(4)小鼠肺内强制表达垂垂蛋白，可引起中性粒细胞渗入并产生粘液。这些结果表明，在支气管哮喘和慢性阻塞性肺疾病的肺组织中，Pendrin被诱导，并参与了这些疾病的粘液产生。纤维化和粘液产生与哮喘和慢性阻塞性肺疾病的发病率和死亡率密切相关。因此，本研究结果有助于了解支气管哮喘和慢性阻塞性肺疾病纤维化和粘液产生的整个分子机制，并开发针对这些表型的治疗试剂。

项目成果

オーダーメイド医療を目指したアレルギー疾患診断の確立

建立过敏性疾病诊断体系，实现个体化医疗

• 发表时间: 2007
• 作者: 松永和人;柳澤悟;市川朋宏;赤松啓一郎;小荒井晃;平野綱彦;杉浦久敏;南方良章;一ノ瀬正和;出原 賢治
• 通讯作者: 出原 賢治

Microarray-based identification of novel biomarkers in asthma.

• DOI: 10.2332/allergolint.55.361
• 发表时间: 2006-12-01
• 期刊: Allergology international : official journal of the Japanese Society of Allergology
• 作者: Izuhara, Kenji;Saito, Hirohisa
• 通讯作者: Saito, Hirohisa

Effect of IL-13 receptor α2 levels on the biological activity of IL-13 variant R110Q

IL-13受体α2水平对IL-13变体R110Q生物活性的影响

• 发表时间: 2007
• 期刊: J Allergy Clin Immunol 120
• 作者: Kanaji;S;Kanaji S;Izuhara K;Nakao I;Izuhara K;Andrews AL
• 通讯作者: Andrews AL

Expression of human IL-13 receptor α2 extracellular domain in Pichia pastoris

人IL-13受体α2胞外结构域在毕赤酵母中的表达

• 发表时间: 2007
• 期刊: Protein Expres Purif 56
• 作者: Kanaji;S;Kanaji S;Izuhara K;Nakao I;Izuhara K;Andrews AL;Hayashi N;Kanaji S;Ohkuri T
• 通讯作者: Ohkuri T

Involvement of periostin, an anion transporter in mucus hyperproduction of bronchial asthma

阴离子转运蛋白骨膜素参与支气管哮喘粘液过度产生

• 发表时间: 2007
• 作者: Izuhara;K
• 通讯作者: K