Identification of atopy genes and analyses of their functions

特应性基因的鉴定及其功能分析

• 批准号: 11670323
• 负责人: IZUHARA Kenji
• 金额: $ 2.3万
• 依托单位: Saga Medical School (2000)Kyushu University (1999)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670323/
• 关键词: interleukin-13; allergy; single nucleotide polymorphism; bronchial asthma; signal transduction; interleukin-13 receptor; Tyk2; STAT3; インターロイキン4; 気道

We investigated the genetic role of the IL-13 gene in the pathogenesis of allergic diseases. We found a novel single nucleotide polymorphism (SNP) which substitutes glutamine at 110 for arginine. The incidence of glutamine was higher than arginine in both atopic and non-atopic asthma patients. Serum level of IL-13 was also higher in the glutamine type. These results suggest that the IL-13 gene is an asthma-causing gene.To identify the target cells of IL-13 in lung, we generated anti-IL-13Rα1 antibody, and performed immunohistochemistry. It turned out that IL- 13Rα1 and IL-4Rα, both of which are the components of the IL-13R highly expressed on bronchial epithelial cells and bronchial smooth muscle cells. These results showed that these cells are main target cells of IL-13 in the lung tissue.We next analyzed the signal transduction mechanism of IL-13 using various types of IL- 13Rα1. Consequently, it was revealed that Tyk2 bound to the Box1 region close to its transmembrane domain, IL-13 activated STAT3 in addition to STAT6, and STAT3 bound to the tyrosine residues close to its C-terminus.

我们研究了IL-13基因在过敏性疾病发病机制中的遗传作用。我们发现了一个新的单核苷酸多态性（SNP），它取代精氨酸110谷氨酰胺。在过敏性和非过敏性哮喘患者中，谷氨酰胺的发生率均高于精氨酸。血清IL-13水平在谷氨酰胺型中也较高。本研究制备了IL-13受体α1抗体，并进行了免疫组化，以确定IL-13在肺组织中的靶细胞。结果表明，IL-13 R α1和IL-4 R α均为IL-13 R的组分，在支气管上皮细胞和支气管平滑肌细胞上高度表达。这些结果表明，这些细胞是IL-13在肺组织中的主要靶细胞。因此，研究表明Tyk 2与靠近其跨膜结构域的Box 1区域结合，IL-13除了STAT 6之外还激活STAT 3，而STAT 3与靠近其C末端的酪氨酸残基结合。

项目成果

Izuhara K: "The Signal Transduction via the Interleukin-4 Receptor and Its Correlation with Atopy."Int.J.Mol.Med.. 3. 3-10 (1999)

Izuhara K：“通过白细胞介素 4 受体的信号转导及其与特应性皮炎的相关性。”Int.J.Mol.Med.. 3. 3-10 (1999)

Mitsuyasu H: "Dominant Effect of lle50Val Variant of the Human Interleukin-4 Receptor α Chain in lgE Synthesis."J.Immunol.. 162. 1227-1231 (1999)

Mitsuyasu H：“人白细胞介素 4 受体 α 链的 lle50Val 变体在 lgE 合成中的显着效应。”J.Immunol.. 162. 1227-1231 (1999)

Kojima M: "Direct Effect of Lipopolysaccharide on Prostaglandin E2 Production by Colon Carcinoma through. Nuclear Factor-κB Activation and Cyclooxygenase-2 Induction."Oncogene. 19. 1225-1231 (2000)

Kojima M：“脂多糖通过核因子-κB 激活和环氧化酶-2 诱导对结肠癌前列腺素 E2 产生的直接影响。”Oncogene，19。1225-1231 (2000)

Izukara K: "Recent advances in under standing how interleukin-13 signals are involved in the pathogenesis of bronchial asthma."Arch.Immunol.Therap.Exp.. 48. 505-512 (2000)

Izukara K：“了解白细胞介素 13 信号如何参与支气管哮喘发病机制的最新进展。”Arch.Immunol.Therap.Exp.. 48. 505-512 (2000)

Heinzmann A: "Genetic Variants of IL-13 Signalling and Human Asthma and Atopy."Hum.Mol.Genet.. 9. 549-559 (2000)

Heinzmann A：“IL-13 信号传导的遗传变异与人类哮喘和特应性皮炎。”Hum.Mol.Genet.. 9. 549-559 (2000)