Abstract |
Inhibitors of alanyl-aminopeptidase e.g. phebestin increase the expression of transforming growth factor (TGF)-beta1 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-beta1 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-beta1 and FoxP3 expression of natural regulatory T-cells.
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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 |
Journal | International journal of molecular medicine
(Int J Mol Med)
Vol. 20
Issue 4
Pg. 483-92
(Oct 2007)
ISSN: 1107-3756 [Print] Greece |
PMID | 17786278
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CD4 Antigens
- Forkhead Transcription Factors
- Foxp3 protein, mouse
- Interleukin-2 Receptor alpha Subunit
- Oligopeptides
- RNA, Messenger
- Transforming Growth Factor beta1
- phebestin
- CD13 Antigens
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Topics |
- Animals
- CD13 Antigens
(antagonists & inhibitors)
- CD4 Antigens
(metabolism)
- Colitis
(enzymology, pathology)
- Female
- Forkhead Transcription Factors
(genetics, metabolism)
- Gene Expression Regulation
(drug effects)
- Humans
- Immune Tolerance
(drug effects)
- Interleukin-2 Receptor alpha Subunit
(metabolism)
- Lymphocyte Activation
(drug effects)
- Mice
- Mice, Inbred BALB C
- Oligopeptides
(pharmacology)
- Phenotype
- RNA, Messenger
(genetics, metabolism)
- T-Lymphocytes, Regulatory
(cytology, drug effects, enzymology)
- Transforming Growth Factor beta1
(genetics, metabolism)
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