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- Title
Galectin-2 induces apoptosis of lamina propria T lymphocytes and ameliorates acute and chronic experimental colitis in mice.
- Authors
Paclik, Daniela; Berndt, Uta; Guzy, Claudia; Dankof, Anja; Danese, Silvio; Holzloehner, Pamela; Rosewicz, Stefan; Wiedenmann, Bertram; Wittig, Bianca M.; Dignass, Axel U.; Sturm, Andreas
- 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.
- Subjects
IMMUNE system; APOPTOSIS; CELL death; IMMUNOHISTOCHEMISTRY; SODIUM sulfate; T cells
- Publication
Journal of Molecular Medicine, 2008, Vol 86, Issue 12, p1395
- ISSN
0946-2716
- Publication type
Article
- DOI
10.1007/s00109-007-0290-2