Targeted disruption of the galectin-3 gene results in decreased susceptibility to multiple low dose streptozotocin-induced diabetes in mice

E. P K Mensah-Brown, Z. Al Rabesi, A. Shahin, M. Al Shamsi, N. Arsenijevic, D. K. Hsu, Fu-Tong Liu, M. L. Lukic

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Galectin 3 (Gal-3) is an antiapoptotic and a proinflammatory lectin. We hypothesized that the proinflammatory properties of Gal-3 may influence disease induction in the multiple low doses of streptozotocin model of diabetes. Diabetes was induced in C57BL/6 Gal-3+/+ and Gal-3-/- mice and disease monitored by blood glucose level, immuno-histology, insulin content of islets and expression of the proinflammatory cytokines, TNF-α, IFN-γ, IL-17, and iNOS in pancreatic lymph nodes. Gal-3+/+ mice developed delayed and sustained hyperglycemia, mononuclear cellular infiltration and reduced insulin content of islets accompanied with expression of proinflammatory cytokines. Gal-3-/- mice were relatively resistant to diabetogenesis as evaluated by glycemia, quantitative histology and insulin content. Further, we observed the weaker expression of IFN-γ and complete absence of TNF-α, and IL-17 in draining pancreatic lymph nodes. Macrophages, the first cells that infiltrate the islet in this model of diabetes, produce less TNF-α and NO in Gal-3-/- mice. Thus, Gal-3 is involved in immune mediated β cell damage and is required for diabetogenesis in this model of disease.

Original languageEnglish (US)
Pages (from-to)83-88
Number of pages6
JournalClinical Immunology
Volume130
Issue number1
DOIs
StatePublished - Jan 2009

Keywords

  • Autoimmunity;
  • Inducible nitric oxide synthase;
  • Interferon-gamma;
  • Interleukin-17
  • Proinflammatory cytokines;

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Mensah-Brown, E. P. K., Al Rabesi, Z., Shahin, A., Al Shamsi, M., Arsenijevic, N., Hsu, D. K., Liu, F-T., & Lukic, M. L. (2009). Targeted disruption of the galectin-3 gene results in decreased susceptibility to multiple low dose streptozotocin-induced diabetes in mice. Clinical Immunology, 130(1), 83-88. https://doi.org/10.1016/j.clim.2008.08.024