IL-10 gene expression is controlled by the transcription factors Sp1 and Sp3

IL-10 is an 18-kDa cytokine with a key role in homeostatic control of infla mmatory and immune responses. We have investigated how transcription of the IL-10 gene is regulated, so as to be able to understand the circumstances of IL-10 expression in both health and disease. In the mouse, IL-10 gene ex pression is regulated by a TATA-type promoter with a critical cis-acting el ement containing GGA repeats located at -89 to -77. Its complementary seque nce is similar to the cis-acting elements (TCC repeats) in the promoters of genes encoding epidermal growth factor receptor and Cuss, All these elemen ts comprise a common CCTCCT sequence with less conserved C + T-rich sequenc es, Eliminating this CCTCCT sequence results in a marked reduction in promo ter activity, suggesting a necessary role in IL-10 gene expression. Despite its dissimilarity to the G + C-rich Spl consensus sequence (GC box), Sp1 a nd Sp3 transcription factors could be shown to bind to this motif, The requ irement for Sp1 and Sp3 in transcription of IL-10 was confirmed using Droso phila SL2 cells, which lack endogenous Sp factors. These results suggest th at the transcription of IL-10 is positively regulated by both Sp1 and Sp3.