association of single nucleotide polymorphisms in the il-18 gene with production of il-18 protein by mononuclear cells from healthy donors协会的地震-基因的单核苷酸多态性与生产地震-蛋白质的单核细胞健康的捐赠者.pdfVIP

Hindawi Publishing Corporation Mediators of Inflammation Volume 2008, Article ID 309721, 6 pages doi:10.1155/2008/309721 Research Article Association of Single Nucleotide Polymorphisms in the IL-18 Gene with Production of IL-18 Protein by Mononuclear Cells from Healthy Donors O. P. Khripko,1 N. S. Sennikova,1 J. A. Lopatnikova,1 J. I. Khripko,2 M. L. Filipenko,2 E. A. Khrapov,2 E. L. Gelfgat,1 E. V. Yakushenko,1 V. A. Kozlov,1 and S. V. Sennikov1 1 Laboratory of Molecular Immunology, Institute of Clinical Immunology , Siberian Branch of Russian Academy of Medical Sciences (SB RAMS), Novosibirsk 630099, Russia 2 Pharmacogenomic Group, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia Correspondence should be addressed to S. V. Sennikov, ici@online.nsk.su Received 24 June 2008; Accepted 5 September 2008 Recommended by Magdalena Klink IL-18 has proinflammatory effects and participates in both innate and adaptive cellular and humoral immunity. A number of SNPs that influence IL-18 production are found in the gene promoter region. We investigated the association of SNPs in the IL-18 promoter at −607 and −137 with the level of IL-18 protein production by PBMC from healthy donors from Southwestern Siberia. The genetic distribution of these SNPs in the promoter site was established by PCR. IL-18 protein production was determined by ELISA. Our results showed that PBMC from donors carrying allele 137C have lower levels of both spontaneous and LPS-stimulated IL-18 production. In contrast, PBMC from donors carrying allele 607A showed significant increases in spontaneous and stimulated IL-18 production compared to wild type. Our study suggests that the SNPs −607 and −137 in the promoter region of the IL-18 gene influence the level of IL-18 protein production by