IFN regulatory factor 4 participates in the human T cell lymphotropic virus type I-mediated activation of the IL-15 receptor alpha promoter.

نویسندگان

  • Jennifer M Mariner
  • Yael Mamane
  • John Hiscott
  • Thomas A Waldmann
  • Nazli Azimi
چکیده

IL-15Ralpha mRNA and protein levels are increased in human T cell lymphotropic virus type-I (HTLV-I)-associated adult T cell leukemia. Previously, we demonstrated that IL-15Ralpha expression was activated by HTLV-I Tax, in part, through the action of NF-kappaB. However, there appeared to be additional motifs within the IL-15Ralpha promoter that were responsive to HTLV-I Tax. In this study, we demonstrated that IL-15Ralpha mRNA expression was activated in human monocytes by IFN treatment, suggesting a role for IFN regulatory factors (IRFs) in IL-15Ralpha transcription. In addition, an IRF element within the Tax-responsive element of the IL-15Ralpha promoter was necessary for maximal Tax-induced activation of this promoter. Furthermore, we demonstrated that IRF-4, a transcription factor known to be elevated in HTLV-I-infected cells, activated the IL-15Ralpha promoter. Inhibition of IRF-4 action lead to reduced Tax-induced activation of the IL-15Ralpha promoter, while inhibition of both IRF-4 and NF-kappaB severely inhibited the Tax-induced activation of this promoter. These findings suggest a role for both NF-kappaB and IRF-4 in the transcriptional regulation of IL-15Ralpha by HTLV-I Tax. It is possible that the HTLV-I Tax-mediated induction of IL-15Ralpha and IL-15 may lead to an autocrine cytokine-mediated stimulatory loop leading to the proliferation of HTLV-I infected cells. This loop of proliferation may facilitate viral propagation and play a role in HTLV-I-mediated disease progression.

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IFN Regulatory Factor 4 Participates in the Human T Cell Lymphotropic Virus Type I-Mediated Activation of the IL-15 Receptor Promoter

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عنوان ژورنال:
  • Journal of immunology

دوره 168 11  شماره 

صفحات  -

تاریخ انتشار 2002