Mosaics of gene variations in the Interleukin-10 gene promoter affect interleukin-10 production depending on the stimulation used

Mörmann, Maik; Rieth, H; Hua, T D; Assohou, C; Roupelieva, Maria; Hu, Shijia; Kremsner, Peter G.; Luty, Adrian J. F.; Kube, Dieter

doi:10.1038/sj.gene.6364073

Cited by 86 publications

(94 citation statements)

References 39 publications

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“…Carriage of the IL-10 À6752T and IL-10 À597C alleles was associated with an increased IL-10 production, implying that a high capability of IL-10 production protects from melanoma development. 20,32,33 Indeed, this is in line with most other publications regarding IL-10 polymorphisms and melanoma. [22][23][24][26][27][28] In contrast, Nagano et al 34 reported that 'low-expression' IL-10 polymorphisms significantly protected from non-melanoma skin cancer.…”

Section: Methodssupporting

confidence: 90%

“…The allelic and genotypic comparison of IL-10 production by lipopolysaccharide (LPS)-stimulated leukocytes with the distal IL-10 À6752AT and IL-10 À6208CG polymorphisms revealed that the IL-10 À6752T and IL-10 À6208C genotypes can be considered as 'high IL-10-producing' genotypes. 20 Unfortunately, the IL-10 À3538AT polymorphism has not been assessed separately with regard to IL-10 production so far. This indicates complex and interactive relations between IL-10 polymorphisms and the capability of IL-10 production, rendering it difficult to ascribe a certain production capacity to a single IL-10 SNP.…”

Section: Introductionmentioning

confidence: 99%

“…This indicates complex and interactive relations between IL-10 polymorphisms and the capability of IL-10 production, rendering it difficult to ascribe a certain production capacity to a single IL-10 SNP. 20 Both low and high IL-10-producing genotypes have been linked to susceptibility of cancer or unfavourable outcome. 21 However, conflicting data are presented, when comparing different studies with respect to melanoma.…”

Section: Introductionmentioning

confidence: 99%

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Distal and proximal interleukin (IL)-10 promoter polymorphisms associated with risk of cutaneous melanoma development: a case–control study

Schoof

Bonin

König³

et al. 2009

Genes Immun

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Section: Methodssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Distal and proximal interleukin (IL)-10 promoter polymorphisms associated with risk of cutaneous melanoma development: a case–control study

Schoof

Bonin

König³

et al. 2009

Genes Immun

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“…45 More recently, different proximal and distal polymorphism effects on IL-10 production have provided a more complex picture of gene expression. 51 Concurrently, HCV treatment and IL10 candidate gene studies have suggested an association of extended haplotypes in the promoter region. [38][39][40][41] As a test of these hypotheses, we performed a separate analysis using the well-studied proximal 46 and distal haplotypes 45 (Table 4).…”

Section: Discussionmentioning

confidence: 99%

Single nucleotide polymorphisms and haplotypes in the IL10 region associated with HCV clearance

et al. 2005

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Hepatitis C virus (HCV) is an infectious blood-borne pathogen that usually persists as a chronic infection. However, approximately 15% of the time, patients can clear the virus, indicating that host differences could be critical in determining the course of HCV infection. The inflammatory response is crucial to resolving or failing to resolve an acute HCV infection. Some previous reports have implicated interleukin 10 (IL10) polymorphisms with successful anti-HCV therapy and natural viral clearance. We tested 54 single nucleotide polymorphisms (SNPs) in the IL10 region (7300 kb and 24 within the IL10 gene itself), which contains 13 genes including the IL10 immunomodulatory paralogs IL19, IL20, and IL24, for association with HCV clearance vs persistence. SNPs from two haplotype block regions, one at IL10 and the other from IL19/IL20, were associated with HCV clearance in African Americans (91 clearance cases and 183 chronically infected matched controls; P ¼ 0.05-0.002) while with expectation-maximization algorithm-reconstructed haplotypes, these associations remained (P ¼ 0.05-0.002). However, no significant associations were detected in European Americans (108 clearance and 245 chronic). Our results indicate that variants of the immunomodulatory IL10 and IL19/IL20 genes may be involved in natural clearance of HCV in the African-American population.

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“…19,20 Changes in the IL-10 gene expression were suggested to be mainly transcriptional and several factor-binding sites that might be involved in the regulation of IL-10 were identified in the IL-10 promoter. [21][22][23][24] The À1087 single nucleotide polymorphism (SNP) is located in one of these sites that was associated with differences in IL-10 gene expression [25][26][27] and the GG genotype of the À1087 SNP was found to be associated with high levels of IL-10 production. 26,27 Recently, we reported that the PU.1, Spi-B and Sp1transcription factors bound to the À1087 SNP in Bcells.…”

Section: Introductionmentioning

confidence: 99%

Sp1 binds to the G allele of the−1087 polymorphism in the IL-10 promoter and promotes IL-10 mRNA transcription and protein production

2010

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Interleukin (IL)-10 is an important cytokine in immune regulation and promotes B-cell proliferation and antibody production. High levels of IL-10 were found in subjects with autoimmune diseases. The A to G single nucleotide polymorphism at -1087 of the IL-10 promoter is associated with differences in promoter activity and IL-10 production. The objectives of this study were to analyze differences in the transcription factor binding to the -1087 IL-10 gene polymorphism in B-cells, the influence of the A to G transition on the IL-10 and Sp1 gene expression in B-cells after lipopolysaccharide (LPS) stimulation and the effect of knockdown of Sp1 on IL-10 gene expression. Using B-cell lines obtained from subjects with GG and AA genotypes for the À1087 polymorphism and chromatin immunoprecipitation assay, we showed that the transcription factors PU.1 and Spi-B bound to both G and A alleles, whereas the transcription factor Sp1 only bound to the G allele. LPS stimulation of the B-cells resulted in a larger increase in IL-10 and Sp1 gene expression for GG genotypes than AA genotypes and knockdown of Sp1 gene expression resulted in a decrease in IL-10 mRNA transcription. IL-10 production was higher for the GG genotype than for the AA genotype.

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Mosaics of gene variations in the Interleukin-10 gene promoter affect interleukin-10 production depending on the stimulation used

Cited by 86 publications

References 39 publications

Distal and proximal interleukin (IL)-10 promoter polymorphisms associated with risk of cutaneous melanoma development: a case–control study

Distal and proximal interleukin (IL)-10 promoter polymorphisms associated with risk of cutaneous melanoma development: a case–control study

Single nucleotide polymorphisms and haplotypes in the IL10 region associated with HCV clearance

Sp1 binds to the G allele of the−1087 polymorphism in the IL-10 promoter and promotes IL-10 mRNA transcription and protein production

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