Sp1 binds to the G allele of the-1087 polymorphism in the IL-10 promoter and promotes IL-10 mRNA transcription and protein production.
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.
Larsson
L
L
Department of Periodontology, The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
Rymo
L
L
Berglundh
T
T
D000483:Alleles; D001402:B-Lymphocytes / Q000378:metabolism; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000378:metabolism; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D000099232:Proto-Oncogene Protein Spi-1
D016753:Interleukin-10; D008070:Lipopolysaccharides; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1