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

Summary 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.