The combined effect of interleukin (IL)-10 and IL-12 polymorphisms on induced cytokine production

被引:30
作者
Miteva, Lyuba [1 ]
Stanilova, Spaska [1 ]
机构
[1] Trakia Univ, Fac Med, Dept Mol Biol Immunol & Med Genet, Stara Zagora, Bulgaria
关键词
-1082A*G IL-10; polymorphism; +16974A*C IL-12B polymorphism; combined effect; IL-12p40; production; IL-10;
D O I
10.1016/j.humimm.2008.07.008
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Interleukin (IL)-12 and IL-10 are immunoregutatory cytokines with an antagonistic effect of the T-helper (Th)1/Th2 cytokine balance and provide a functional link between innate and adaptive immune responses. The aim of the study was to investigate the combined effect of -1082A*G in IL10 and +16974A*C in IL12B single nucleotide polymorphisms (SNPs) on induced cytokine production by stimulated peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. The presence of the high-producer IL-12p40 genotype led to diminished production of IL-10 as determined by the -1082*G allele of SNIP in IL10. Significantly decreased IL-10 production was detected in AA+AG/GG in comparison with the low-producer IL-12p40 (AC/CC+AG/GG) genotype combination after stimulation with C3bgp (2 4 vs. 29 +/- 14.2 pg/ml; p = 0.0003) and LPS (33.4 +/- 13.5 vs. 93.3 +/- 59.6 pg/ml; p = 0.019). IL-12p40 production was independent of IL10 genotype. The present results demonstrated that the production of IL-10 from PBMC depended on both -1082A*G in IL10 and +16974A*C in IL12B polymorphisms. (C) 2008 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:562 / 566
页数:5
相关论文
共 26 条
[1]  
Aste-Amezaga M, 1998, J IMMUNOL, V160, P5936
[2]   Cytokine polymorphism frequencies in the Greek Cypriot population [J].
Costeas, PA ;
Koumas, L ;
Koumouli, A ;
Kyriakou-Giantsiou, A ;
Papaloizou, A .
EUROPEAN JOURNAL OF IMMUNOGENETICS, 2003, 30 (05) :341-343
[3]  
Crawley E, 1999, ARTHRITIS RHEUM-US, V42, P1101, DOI 10.1002/1529-0131(199906)42:6<1101::AID-ANR6>3.0.CO
[4]  
2-Y
[5]   New polymorphisms in the IL-10 promoter region [J].
D'Alfonso, S ;
Rampi, M ;
Rolando, V ;
Giordano, M ;
Momigliano-Richiardi, P .
GENES AND IMMUNITY, 2000, 1 (03) :231-233
[6]   PRODUCTION OF NATURAL-KILLER-CELL STIMULATORY FACTOR (INTERLEUKIN-12) BY PERIPHERAL-BLOOD MONONUCLEAR-CELLS [J].
DANDREA, A ;
RENGARAJU, M ;
VALIANTE, NM ;
CHEHIMI, J ;
KUBIN, M ;
ASTE, M ;
CHAN, SH ;
KOBAYASHI, M ;
YOUNG, D ;
NICKBARG, E ;
CHIZZONITE, R ;
WOLF, SF ;
TRINCHIERI, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 176 (05) :1387-1398
[7]   Microsatellite alleles and single nucleotide polymorphisms (SNP) combine to form four major haplotype families at the human interleukin-10 (IL-10) locus [J].
Eskdale, J ;
Keijsers, V ;
Huizinga, T ;
Gallagher, G .
GENES AND IMMUNITY, 1999, 1 (02) :151-155
[8]   Interleukin 10 secretion in relation to human IL-10 locus haplotypes [J].
Eskdale, J ;
Gallagher, G ;
Verweij, CL ;
Keijsers, V ;
Westendorp, RGJ ;
Huizinga, TWJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (16) :9465-9470
[9]   Mapping of the human IL10 gene and further characterization of the 5′ flanking sequence [J].
Eskdale, J ;
Kube, D ;
Tesch, H ;
Gallagher, G .
IMMUNOGENETICS, 1997, 46 (02) :120-128
[10]   Genetic polymorphism of IL-12 p40 gene in immune-mediated disease [J].
Hall, MA ;
McGlinn, E ;
Coakley, G ;
Fisher, SA ;
Boki, K ;
Middleton, D ;
Kaklamani, E ;
Moutsopoulos, H ;
Loughran, TP ;
Ollier, WER ;
Panayi, GS ;
Lanchbury, JS .
GENES AND IMMUNITY, 2000, 1 (03) :219-224