Analyses of a cation transporters during immune and inflammatory responses

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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.