Analyses of a cation transporters during immune and inflammatory responses

最近的遗传学研究表明，阳离子转运蛋白SLC22A4与免疫和炎症疾病有关。我们报道了一个单核苷酸多态性，SNP，与日本类风湿关节炎。Peltekova V.等人还报道了SLC22A4上的非同义SNP和SLC22A5上的SNP与克罗恩病相关，该SNP与前一SNP具有强连锁不平衡。由于类风湿性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很可能参与了这些反应，因此我们试图分析SLC 22 A4在免疫和炎症条件下的功能。我们还尝试通过调控内源性SLC22A4的功能来控制这些反应。转运蛋白的可能底物之一是麦角硫因。然而，我们不知道麦角硫因的半衰期和代谢。因此，我们建立了瞬态以及本构击倒系统。我们还通过质粒载体法和逆转录病毒载体法将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。

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.