The Sp1 transcription factor binds to the G-allele of the -1087 IL-10 gene polymorphism and enhances transcriptional activation.
The objectives of this study were to evaluate the influence of the -1087 single nucleotide polymorphism (SNP) on the gene expression of interleukin (IL)-10 and to identify transcription factors binding to this site in B cells. Using electrophoretic mobility-shift assays and nuclear extract from the DG75 B-cell line, we demonstrated that the Sp1 transcription factor bound to the -1087 G-allele of the IL-10 promoter and that the transcription factors PU.1 and Spi-B bound to both the G- and A-alleles. Transient transfections showed that lipopolysaccharide stimulation resulted in a 15-fold increase in promoter activity for the G-allele as compared to a 6-fold increase for the A-allele. Co-transfection with Sp1 expression vector in Sp1-deficient SL2 cells leading to Sp1 binding to the G-allele of the -1087 SNP resulted in increased IL-10 promoter activity. The results suggest a role for Sp1 transcription factor in the activation of IL-10 through the G-allele of the -1087 SNP in response to inflammatory signals.
Larsson
L
L
Department of Periodontology, The Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden.
Johansson
P
P
Jansson
A
A
Donati
M
M
Rymo
L
L
Berglundh
T
T
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D000099232:Proto-Oncogene Protein Spi-1
D004268:DNA-Binding Proteins; D016753:Interleukin-10; D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C076877:SPIB protein, human