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Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
IL-10 is an 18-kDa cytokine with a key role in homeostatic control of inflammatory 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 expression is regulated by a TATA-type promoter with a critical cis-acting element containing GGA repeats located at -89 to -77. Its complementary sequence is similar to the cis-acting elements (TCC repeats) in the promoters of genes encoding epidermal growth factor receptor and CD58. All these elements comprise a common CCTCCT sequence with less conserved C + T-rich sequences. Eliminating this CCTCCT sequence results in a marked reduction in promoter activity, suggesting a necessary role in IL-10 gene expression. Despite its dissimilarity to the G + C-rich Sp1 consensus sequence (GC box), Sp1 and Sp3 transcription factors could be shown to bind to this motif. The requirement for Sp1 and Sp3 in transcription of IL-10 was confirmed using Drosophila SL2 cells, which lack endogenous Sp factors. These results suggest that the transcription of IL-10 is positively regulated by both Sp1 and Sp3.
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S. Tavor, P. T. Vuong, D. J. Park, A. F. Gombart, A. H. Cohen, and H. P. Koeffler Macrophage functional maturation and cytokine production are impaired in C/EBPepsilon -deficient mice Blood, March 1, 2002; 99(5): 1794 - 1801. [Abstract] [Full Text] [PDF]
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M. J. Powell, S. A. J. Thompson, Y. Tone, H. Waldmann, and M. Tone Posttranscriptional Regulation of IL-10 Gene Expression Through Sequences in the 3'-Untranslated Region J. Immunol., July 1, 2000; 165(1): 292 - 296. [Abstract] [Full Text] [PDF]
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