A role for mitogen-activated protein kinase and Ets-1 in the induction of interleukin-10 transcription by human immunodeficiency virus-1 Tat.
The human immunodeficiency virus (HIV) Tat protein has multiple regulatory roles, including trans-activation of the HIV genome and regulation of immune signalling processes, including kinase activation and cytokine expression. We recently demonstrated that HIV-1 Tat induces the expression of interleukin (IL)-10 via p38 mitogen-activated protein kinase (MAPK) activation. We further delineated that the Tat-responsive element of the IL-10 promoter was located within 625 to 595 bp upstream from the transcription start site. Using electrophoretic mobility shift assays, the transcription factors Ets-1 and Sp-1 were shown to bind to the IL-10 promoter to activate transcription of the gene. Furthermore, sequential deletional mutations of the Ets-1- and Sp-1-binding sites in the -625/-595 region reduced the DNA binding and transcription activity of the IL-10 promoter. Our results also showed that both the Tat-induced and Ets-1-regulated IL-10 promoter-driven luciferase activity can be abrogated by inhibitors of the p38 MAPK activity. In conclusion, the coordinated activities of p38 MAPK and the transcription factors, Ets-1 and Sp-1, may play an important role in the HIV-1 Tat-induced IL-10 transcription.
Li
James C B
JC
Department of Paediatrics and Adolescent Medicine and Bio-Screening Unit, Li Ka Shing Faculty of Medicine, Teh University of Hong Kong, Hong Kong, China.
Lau
Allan S Y
AS
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D015696:Gene Products, tat / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000276:immunology; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus
D004268:DNA-Binding Proteins; C494041:ETS1 protein, human; D015696:Gene Products, tat; D050784:Proto-Oncogene Protein c-ets-1; D011994:Recombinant Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D016753:Interleukin-10; D048051:p38 Mitogen-Activated Protein Kinases