The AT-rich region between -54 to -66 is important for the promoter activity of interleukin-10 in Epstein-Barr virus positive Burkitt's lymphoma cells.
IL-10 is an important regulatory cytokine. The recent characterization of the 5'-flanking region of IL-10 led to the identification of the promoter region. The infection of B cells with EBV induces IL-10 production which may contribute to EBV-induced transformation. In the present report, IL-10 promoter elements involved in the constitutive expression of IL-10 in EBV-positive lymphoma cells are described. The AT-rich region between -54/-66 from the transcriptional start site was found to be important for IL-10-promoter activity in BL36. A point mutation at position -60 (T/A) was associated with over 90% reduction of luciferase activity in the cell lines BL36 and BL74. The conversion of A/T at position -57 led to enhanced promoter activity. In addition the AT-rich region could serve as an enhancer for the beta-globin basic promoter. In BJAB cells (EBV-negative), sequences between -205/-139 rather than the AT-rich region were involved in IL-10 promoter regulation. This underlines the importance of the AT-rich region for EBV-associated IL-10 promoter regulation. Our results further the understanding of how the IL-10 gene could be regulated in B cell lymphomas.
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Universität zu Köln, Klinik für Innere Medizin I, Zentrum für Molekulare Medizin Köln. dieter.kube@uni-tuebingen.de
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von Knethen
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D020856:AT Rich Sequence / Q000235:genetics*; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000821:virology; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D009841:Oligonucleotides; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D009841:Oligonucleotides; D016753:Interleukin-10