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

Genes & Immunity volume 11, pages 181–187 (2010)Cite this article

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Abstract

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 −1087 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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Authors and Affiliations

  1. Department of Periodontology, The Sahlgrenska Academy, University of Gothenburg, G, ö, teborg, Sweden

    L Larsson & T Berglundh

  2. Department of Clinical Chemistry and Transfusion Medicine, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, G, ö, teborg, Sweden

    L Rymo

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Correspondence to T Berglundh.

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Larsson, L., Rymo, L. & Berglundh, T. Sp1 binds to the G allele of the−1087 polymorphism in the IL-10 promoter and promotes IL-10 mRNA transcription and protein production. Genes Immun 11, 181–187 (2010). https://doi.org/10.1038/gene.2009.103

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