A role for mitogen-activated protein kinase and Ets-1 in the induction of interleukin-10 transcription by human immunodeficiency virus-1 Tat

Immunology. 2007 Jul;121(3):337-48. doi: 10.1111/j.1365-2567.2007.02580.x. Epub 2007 Mar 22.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cell Line
  • DNA-Binding Proteins / metabolism
  • Gene Products, tat / immunology*
  • HIV-1 / immunology*
  • HeLa Cells
  • Humans
  • Interleukin-10 / genetics*
  • Promoter Regions, Genetic / immunology
  • Proto-Oncogene Protein c-ets-1 / genetics
  • Proto-Oncogene Protein c-ets-1 / immunology
  • Recombinant Proteins / immunology
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Transcription, Genetic / immunology*
  • p38 Mitogen-Activated Protein Kinases / immunology
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • DNA-Binding Proteins
  • ETS1 protein, human
  • Gene Products, tat
  • Proto-Oncogene Protein c-ets-1
  • Recombinant Proteins
  • tat Gene Products, Human Immunodeficiency Virus
  • Interleukin-10
  • p38 Mitogen-Activated Protein Kinases