Abstract | BACKGROUND:
Dipeptidyl peptidase IV (DP IV, CD26) and DP IV-like enzymes, such as dipeptidyl peptidase II (DP II), dipeptidyl peptidase 8 (DP8), and dipeptidyl peptidase 9 (DP9), have been recognized to regulate T lymphocyte activation. Lys[Z(NO2)]-thiazolidide (LZNT) and Lys[Z(NO2)]-pyrrolidide (LZNP), non-selective inhibitors of DP IV-like activity known to target DP IV as well as DP II, DP8, and DP9, suppress T lymphocyte proliferation in vitro. Moreover, these inhibitors are capable of attenuating the severity of autoimmune diseases, such as experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis, and experimental arthritis, a model of human rheumatoid arthritis, in vivo, particularly in combination with inhibitors of aminopeptidase N (APN, CD13) enzymatic activity. METHODS: Here, we studied the influence of non-selective and selective inhibitors of DP IV-like enzymes on DNA synthesis in mitogen-stimulated splenocytes from wild-type C57BL/6 mice and DP IV/CD26-knockout (DP IV/CD26-KO) mice. RESULTS: LZNT and LZNP, the non-selective inhibitors of DP IV-like activity, suppressed the DNA synthesis in stimulated splenocytes from wild-type and DP IV/ CD26-KO mice to a comparable extent. Further, a selective inhibitor of DP8/DP9 activity was capable of suppressing DNA synthesis in mitogen-stimulated splenocytes of both wild-type and knockout mice to the same extent. In contrast, selective inhibitors of DP IV and DP II lacked this suppressive activity. CONCLUSIONS: Our data support the hypothesis that DP8 and/or DP9 represent additional pharmacological targets for the suppression of T cell proliferation and for anti-inflammatory therapy.
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Authors | Dirk Reinhold, Alexander Goihl, Sabine Wrenger, Annegret Reinhold, Ulrike C Kühlmann, Jürgen Faust, Klaus Neubert, Anja Thielitz, Stefan Brocke, Michael Täger, Siegfried Ansorge, Ute Bank |
Journal | Clinical chemistry and laboratory medicine
(Clin Chem Lab Med)
Vol. 47
Issue 3
Pg. 268-74
( 2009)
ISSN: 1434-6621 [Print] Germany |
PMID | 19676138
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Pyrrolidines
- Thiazoles
- lysyl-(Z(nitro))pyrrolidide
- lysyl-(Z(nitro))thiazolidide
- DNA
- Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
- dipeptidyl peptidase II
- Dipeptidyl Peptidase 4
- Lysine
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Topics |
- Animals
- Cell Proliferation
(drug effects)
- DNA
(biosynthesis)
- Dipeptidyl Peptidase 4
(deficiency, genetics)
- Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
(antagonists & inhibitors, genetics, immunology)
- Disease Models, Animal
- Lymphocyte Activation
- Lysine
(analogs & derivatives, chemistry, pharmacology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Pyrrolidines
(chemistry, pharmacology)
- Spleen
(cytology, immunology)
- T-Lymphocytes
(drug effects, immunology)
- Thiazoles
(chemistry, pharmacology)
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