Alleles carried at positions ?819 and ?592 of the IL10 promoter affect transcription following stimulation of peripheral blood cells with Streptococcus pneumoniae
- 6 November 2003
- journal article
- research article
- Published by Springer Nature in Immunogenetics
- Vol. 55 (9) , 629-632
- https://doi.org/10.1007/s00251-003-0621-6
Abstract
IL-10 inhibits the production of many pro-inflammatory cytokines. Polymorphisms in the IL10 gene promoter at positions −1082G→A, −819C→T and −592C→A occur as three haplotypes, ATA, GCC and ACC. These influence several infectious and inflammatory diseases including community-acquired pneumonia, where a role for IL-10 is suggested by fluctuations in plasma levels of the cytokine. However, the effects of the haplotypes on IL-10 production are unclear. We stimulated peripheral blood mononuclear cells (PBMC) from at least five individuals homozygous for each of the three haplotypes with lipopolysaccharide (LPS, 10 μg/ml) or heat-killed Streptococcus pneumoniae (107cfu/ml) and measured IL-10 mRNA by RT-PCR. Following S. pneumoniae stimulation, PBMC with the ATA haplotype had higher IL-10 mRNA levels than those with the GCC haplotype at 4 h (independent t-test; P=0.024), or the ACC haplotype at 4 h (PP=0.007). Following LPS stimulation, IL-10 mRNA levels were not significantly influenced by the IL10 haplotype, but similar trends were observed, consistent with the variable outcome of published studies. The results suggest that the −819 and/or −592 alleles affect transcription.Keywords
This publication has 23 references indexed in Scilit:
- Pneumococcal Septic Shock Is Associated with the Interleukin-10–1082 Gene Promoter PolymorphismAmerican Journal of Respiratory and Critical Care Medicine, 2003
- Association of IL-10 polymorphism with severity of illness in community acquired pneumoniaThorax, 2003
- The Influence of Tumor Necrosis Factor–α and Interleukin‐10 Gene Promoter Polymorphism on the Inflammatory Response in Experimental Human EndotoxemiaClinical Infectious Diseases, 2001
- Microsatellite alleles and single nucleotide polymorphisms (SNP) combine to form four major haplotype families at the human interleukin-10 (IL-10) locusGenes & Immunity, 1999
- Polymorphic haplotypes of the interleukin-10 5? flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritisArthritis & Rheumatism, 1999
- High level multiplex genotyping by MALDI-TOF mass spectrometryNature Biotechnology, 1998
- Interleukin 10 secretion in relation to human IL-10 locus haplotypesProceedings of the National Academy of Sciences, 1998
- IL-10 Gene Promoter Polymorphisms in Rheumatoid Arthritis: SHORT REPORTScandinavian Journal of Rheumatology, 1998
- Genetic influence on cytokine production in meningococcal diseaseThe Lancet, 1997
- Isolation of the Human Interleukin 10 Promoter. Characterization of the Promoter Activity in Burkitt's Lymphoma Cell LinesCytokine, 1995