Analyses of a cation transporters during immune and inflammatory responses

免疫和炎症反应过程中阳离子转运蛋白的分析

• 批准号: 18390287
• 负责人: YAMAMOTO Kazuhiko
• 金额: $ 10.77万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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-18390287/
• 关键词: Immunology; genetics; internal medicine; 遺伝学; 関節リウマチ; 疾患関連遺伝子; 有機カチオントランスポーター; SLC22A4; サイトカイン; エルゴチオネイン

Recent genetic studies suggested that an cation transporter, SLC22A4, is associated with immune and inflammatory disorders. We reported a single nucleotide polymorphism, SNP, is associated with Japanese rheumatoid arthritis. Peltekova V. et al also reported that a non-synonymous SNP on SLC22A4 and a SNP on SLC22A5 that is strong linkage disequilibrium to the former SNP is associated with Crohn's disease. Since rheumatoid arthritis and Crohn's disease are immune and inflammatory disorders, it is highly possible that such cation transporters are involved in the reactions.We thus tried to analyze the function of SLC22A4 in the immune and inflammatory conditions. We also tried to find out the ways to control the reactions by modulating the function of SLC22A4.We made first siRNAs to knock down endogenous SLC22A4. One of the possible substrates of the transporter is ergothioneine. However, we do not know the half life and metabolism of ergothioneine. Thus we set up transient as well as constitutive knock down systems. We also introduce the SLC22A4 gene into cells by plasmid vector methods and retrovial vectors. We are now examining the possible role of SLC22A4 on cytokine expressions using these SLC22A4 modified cells.

最近的遗传学研究表明，一种阳离子转运体SLC22A4与免疫和炎症疾病有关。我们报道了一种单核苷酸多态性（SNP）与日本类风湿性关节炎有关。Peltekova V.等人也报道了SLC22A4上的非同义SNP和SLC22A5上与前者SNP有强连锁不平衡的SNP与克罗恩病相关。由于类风湿关节炎和克罗恩病是免疫和炎症性疾病，这些阳离子转运蛋白极有可能参与了这些反应。因此，我们试图分析SLC22A4在免疫和炎症条件下的功能。我们也试图找到通过调节SLC22A4的功能来控制反应的方法。我们制作了第一个敲除内源性SLC22A4的sirna。麦角硫因是该转运体可能的底物之一。但麦角硫因的半衰期和代谢情况尚不清楚。因此，我们建立了暂态和本构击倒系统。我们还通过质粒载体法和逆转录载体法将SLC22A4基因导入细胞。我们现在正在使用这些SLC22A4修饰的细胞研究SLC22A4对细胞因子表达的可能作用。

项目成果

Splenic dendritic cells induced by oral antigen administration are important for the transfer of oral tolerance in an experimental model of asthma

• DOI: 10.4049/jimmunol.176.3.1481
• 发表时间: 2006-02-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Nagatani, K;Dohi, M;Yamamoto, K
• 通讯作者: Yamamoto, K

Antigen-specific immunotherapy for autoimmune diseases

• DOI: 10.1517/14712598.7.3.359
• 发表时间: 2007-02
• 期刊: Expert Opinion on Biological Therapy
• 影响因子: 4.6
• 作者: Kazuhiko Yamamoto;A. Okamoto;K. Fujio

Antigen-sensitized CD4+CD62Llow memory/effector T helper 2 cells can induce airway hyperresponsiveness in an antigen free setting.

• DOI: 10.1186/1465-9921-6-46
• 发表时间: 2005-05-28
• 期刊: Respiratory research
• 影响因子: 5.8
• 作者: Nakagome K;Dohi M;Okunishi K;To Y;Sato A;Komagata Y;Nagatani K;Tanaka R;Yamamoto K
• 通讯作者: Yamamoto K

Lessons from a Genomewide AssociationStudy of Rheumatoid Arthritis

类风湿关节炎全基因组关联研究的经验教训

• 发表时间: 2007
• 期刊: N Engl Jmed 357
• 作者: Akishi Ooi;Shioto Suzuki;Kumiko Nakazawa;Jun Itakura;Issei Imoto ;Hiroyuki Nakamura;Yoh Dobashi.;成瀬妙子;Yamamoto K.& Yamada R.
• 通讯作者: Yamamoto K.& Yamada R.

Interleukin-17B and interleukin-17C are associated with TNF-alpha production and contribute to the exacerbation of inflammatory arthritis

Interleukin-17B 和 interleukin-17C 与 TNF-α 的产生相关，并导致炎症性关节炎的恶化

• 发表时间: 2007
• 期刊: J Immunol. 179
• 作者: Yamaguchi Y;Fujio K;Shoda H;Okamoto A;Tsuno NH;Takahashi K;Yamamoto K.
• 通讯作者: Yamamoto K.