Galectin-1 suppresses experimental colitis in mice.

Abstract

BACKGROUND & AIMS:

Uncontrolled T-cell activation plays a critical role in the pathogenesis of inflammatory bowel diseases. Therefore, pharmacologic strategies directed to restore the normal responsiveness of the immune system by deleting inappropriately activated T cells could be efficacious in the treatment of these pathologic conditions. Galectin-1 is an endogenous lectin expressed in lymphoid organs that plays a role in the maintenance of central and peripheral tolerance. The aim of the present study was to evaluate the therapeutic effects of galectin-1 on T-helper cell type 1-mediated experimental colitis induced by intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice.

METHODS:

Cells and tissues from mice with TNBS colitis receiving treatment with several doses of human recombinant galectin-1 (hrGAL-1) were analyzed for morphology, cytokine production, and apoptosis.

RESULTS:

Prophylactic and therapeutic administration of rhGAL-1 resulted in a striking improvement in the clinical and histopathologic aspects of the disease. hrGAL-1 reduced the number of hapten-activated spleen T cells, decreased inflammatory cytokine production, and profoundly reduced the ability of lamina propria T cells to produce IFN gamma in vitro. Moreover, hrGAL-1 led to the appearance of apoptotic mononuclear cells in colon tissue when administered in vivo and induced selective apoptosis of TNBS-activated lamina propria T cells in vitro.

CONCLUSION:

Collectively, these data show that hrGAL-1 exerts protective and immunomodulatory activity in TNBS-induced colitis and it might be effective in the treatment of inflammatory bowel diseases.

• Authors: Luca Santucci, Stefano Fiorucci, Natalia Rubinstein, Andrea Mencarelli, Barbara Palazzetti, Barbara Federici, Gabriel A Rabinovich, Antonio Morelli
• Journal: Gastroenterology (Gastroenterology) Vol. 124 Issue 5 Pg. 1381-94 (May 2003) ISSN: 0016-5085 [Print] United States
• PMID: 12730878 (Publication Type: Journal Article)

Chemical References

• Galectin 1
• Interleukin-1
• Recombinant Proteins
• Tumor Necrosis Factor-alpha
• Interleukin-12
• Interferon-gamma
• Trinitrobenzenesulfonic Acid

Topics

• Animals
• CD4-Positive T-Lymphocytes (drug effects, metabolism)
• Colitis (drug therapy, immunology, pathology)
• Disease Models, Animal
• Galectin 1 (genetics, pharmacology)
• Gene Expression (physiology)
• Interferon-gamma (metabolism)
• Interleukin-1 (metabolism)
• Interleukin-12 (metabolism)
• Mice
• Mice, Inbred BALB C
• Recombinant Proteins (pharmacology)
• Spleen (cytology)
• Trinitrobenzenesulfonic Acid
• Tumor Necrosis Factor-alpha (metabolism)