Journal of Molecular Medicine

, Volume 86, Issue 12, pp 1395–1406

Galectin-2 induces apoptosis of lamina propria T lymphocytes and ameliorates acute and chronic experimental colitis in mice

  • Daniela Paclik
  • Uta Berndt
  • Claudia Guzy
  • Anja Dankof
  • Silvio Danese
  • Pamela Holzloehner
  • Stefan Rosewicz
  • Bertram Wiedenmann
  • Bianca M. Wittig
  • Axel U. Dignass
  • Andreas Sturm
Original Article

DOI: 10.1007/s00109-007-0290-2

Cite this article as:
Paclik, D., Berndt, U., Guzy, C. et al. J Mol Med (2008) 86: 1395. doi:10.1007/s00109-007-0290-2
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Abstract

Galectins have recently emerged as central regulators of the immune system. We have previously demonstrated that carbohydrate-dependent binding of galectin-2 induces apoptosis in activated T cells. Here, we investigate the potential therapeutic effect of galectin-2 in experimental colitis. Galectin-2 expression and its binding profile were determined by immunohistochemistry. Acute and chronic colitis was induced by dextran sodium sulfate administration and in a T-cell transfer colitis model. Apoptosis was assessed by TdT-mediated dUTP-biotin nick-end labeling, and cytokine secretion was determined by cytometric bead array. We show that galectin-2 was constitutively expressed mainly in the epithelial compartment of the mouse intestine and bind to lamina propria mononuclear cells. During colitis, galectin-2 expression was reduced, but could be restored to normal levels by immunosuppressive treatment. Galectin-2 treatment induced apoptosis of mucosal T cells and thus ameliorated acute and chronic dextran-sodium-sulfate-induced colitis and in a T-helper-cell 1-driven model of antigen-specific transfer colitis. Furthermore, the pro-inflammatory cytokine release was inhibited by galectin-2 treatment. In preliminary toxicity studies, galectin-2 was well tolerated. Our study provides evidence that galectin-2 induces apoptosis in vivo and ameliorates acute and chronic murine colitis. Furthermore, galectin-2 has no significant toxicity over a broad dose range, suggesting that it may serve as a new therapeutic agent in the treatment of inflammatory bowel disease.

Keywords

Galectins Galectin-2 Apoptosis Inflammatory bowel diseases T lymphocytes 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Daniela Paclik
    • 1
  • Uta Berndt
    • 1
  • Claudia Guzy
    • 1
  • Anja Dankof
    • 2
  • Silvio Danese
    • 3
  • Pamela Holzloehner
    • 4
  • Stefan Rosewicz
    • 1
  • Bertram Wiedenmann
    • 1
  • Bianca M. Wittig
    • 4
  • Axel U. Dignass
    • 1
  • Andreas Sturm
    • 1
    • 5
  1. 1.Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Campus Virchow KlinikumCharité-UniversitätsmedizinBerlinGermany
  2. 2.Institut für Pathologie, Campus MitteCharité-UniversitätsmedizinBerlinGermany
  3. 3.Division of GastroenterologyInstituto Clinico Humanitas-IRCCSMilanItaly
  4. 4.Medizinische Klinik 1 (Gastroenterologie, Infektiologie und Rheumatologie), Campus Benjamin FranklinCharité-UniversitätsmedizinBerlinGermany
  5. 5.Campus Virchow Clinic, Department of Hepatology and GastroenterologyCharité-Universitätsmedizin BerlinBerlinGermany

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