Inhibition of alanyl-aminopeptidase on CD4+CD25+ regulatory T-cells enhances expression of FoxP3 and TGF-β1 and ameliorates acute colitis in mice

  • Authors:
    • Ute Bank
    • Janine Tadje
    • Michael Täger
    • Carmen Wolke
    • Alicja Bukowska
    • Annelore Ittenson
    • Dirk Reinhold
    • Martin Helmuth
    • Siegfried Ansorge
    • Ann Shakespeare
    • Michael Vieth
    • Peter Malfertheiner
    • Michael Naumann
    • Uwe Lendeckel
  • View Affiliations

  • Published online on: October 1, 2007     https://doi.org/10.3892/ijmm.20.4.483
  • Pages: 483-492
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Abstract

Inhibitors of alanyl-aminopeptidase e.g. phebestin increase the expression of transforming growth factor (TGF)-β1 in mononuclear cells. We investigated whether phebestin also produced this effect in CD4+CD25+ T-cells and whether phebestin-treated CD4+CD25+ T-cells were capable of ameliorating acute colitis in mice. The suppressive activity of mouse CD4+CD25+ T-cells was assessed in vitro by co-culture with splenocytes. mRNA expression associated with the suppressive phenotype was determined in vitro and in vivo. The in vivo role of phebestin-exposed CD4+CD25+ T-cells was studied in sodium dextran sulfate-induced acute colitis in mice. The proliferation of activated effector T-cells or splenocytes in vitro was inversely correlated with the number of CD4+CD25+ T-cells. Phebestin pre-treatment substantially enhanced the suppressive activity of these cells and increased expression levels of TGF-β1 and FoxP3. Furthermore, transfer of CD4+CD25+ T-cells exposed to phebestin for a short time ex vivo significantly reduced the mouse colitis disease activity index. We conclude that aminopeptidase inhibitors support the suppressive activity as well as TGF-β1 and FoxP3 expression of natural regulatory T-cells.

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October 2007
Volume 20 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Bank, U., Tadje, J., Täger, M., Wolke, C., Bukowska, A., Ittenson, A. ... Lendeckel, U. (2007). Inhibition of alanyl-aminopeptidase on CD4+CD25+ regulatory T-cells enhances expression of FoxP3 and TGF-β1 and ameliorates acute colitis in mice. International Journal of Molecular Medicine, 20, 483-492. https://doi.org/10.3892/ijmm.20.4.483
MLA
Bank, U., Tadje, J., Täger, M., Wolke, C., Bukowska, A., Ittenson, A., Reinhold, D., Helmuth, M., Ansorge, S., Shakespeare, A., Vieth, M., Malfertheiner, P., Naumann, M., Lendeckel, U."Inhibition of alanyl-aminopeptidase on CD4+CD25+ regulatory T-cells enhances expression of FoxP3 and TGF-β1 and ameliorates acute colitis in mice". International Journal of Molecular Medicine 20.4 (2007): 483-492.
Chicago
Bank, U., Tadje, J., Täger, M., Wolke, C., Bukowska, A., Ittenson, A., Reinhold, D., Helmuth, M., Ansorge, S., Shakespeare, A., Vieth, M., Malfertheiner, P., Naumann, M., Lendeckel, U."Inhibition of alanyl-aminopeptidase on CD4+CD25+ regulatory T-cells enhances expression of FoxP3 and TGF-β1 and ameliorates acute colitis in mice". International Journal of Molecular Medicine 20, no. 4 (2007): 483-492. https://doi.org/10.3892/ijmm.20.4.483