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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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1434-6621
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Volume 47, Issue 3

Issues

Role of dipeptidyl peptidase IV (DP IV)-like enzymes in T lymphocyte activation: investigations in DP IV/CD26-knockout mice

Dirk Reinhold
  • 1Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
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/ Alexander Goihl
  • 2Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
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/ Sabine Wrenger
  • 3Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
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/ Annegret Reinhold
  • 4Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
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/ Ulrike C. Kühlmann
  • 5Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
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/ Jürgen Faust
  • 6Institute of Biochemistry and Biotechnology, Department of Natural Sciences I, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany
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/ Klaus Neubert
  • 7Institute of Biochemistry and Biotechnology, Department of Natural Sciences I, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany
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/ Anja Thielitz
  • 8University Clinic of Dermatology and Venereology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
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/ Stefan Brocke
  • 9Departments of Immunology and Pharmacology, University of Connecticut Health Center, Farmington, CT, USA
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/ Michael Täger / Siegfried Ansorge / Ute Bank
Published Online: 2009-02-10 | DOI: https://doi.org/10.1515/CCLM.2009.062

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.

Clin Chem Lab Med 2009;47:268–74.

Keywords: CD26; dipeptidyl peptidase IV (DP IV); DP IV-like enzymes; T cell activation

About the article

Corresponding author: Prof. Dr. D. Reinhold, Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany Phone: +49-391-6715857, Fax: +49-391-6715852,


Received: 2008-07-11

Accepted: 2008-11-07

Published Online: 2009-02-10

Published in Print: 2009-03-01


Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 47, Issue 3, Pages 268–274, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2009.062.

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