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

• Published in: Clinical immunology (Orlando, Fla. Print) Vol. 130; no. 1; pp. 83 - 88
• Main Authors: Mensah-Brown, E.P.K, Al Rabesi, Z, Shahin, A, Al Shamsi, M, Arsenijevic, N, Hsu, D.K, Liu, F-T, Lukic, M.L
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier Inc 01-01-2009; Elsevier
• Subjects: Allergy and Immunology; Animals; Autoimmunity; Biological and medical sciences; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetes. Impaired glucose tolerance; Disease Susceptibility; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Galectin 3 - deficiency; Galectin 3 - genetics; Galectin 3 - metabolism; Gene Deletion; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Genetic Predisposition to Disease - genetics; Inducible nitric oxide synthase; Interferon-gamma; Interleukin-17; Lipopolysaccharides - pharmacology; Lymph Nodes - drug effects; Lymph Nodes - immunology; Medical sciences; Mice; Mice, Knockout; Nitric Oxide - metabolism; Proinflammatory cytokines; Streptozocin - pharmacology; Autoimmunity; complete Freund's adjuvant; NO; LPS; inducible nitric oxide synthase; tumor necrosis factor-alpha; IFN-γ; MLD-STZ; iNOS; Interleukin-17; interleukin; nuclear factor-κB, RT-PCR, reverse transcriptase polymerase chain reaction; multiple low dose streptozotocin; Interferon-gamma; nitric oxide; interferon gamma; IL; NFκB; EAE; lipopolysaccharide, mRNA, messenger ribonucleic acid; experimental allergic encephalomyelitis; Gal; TNF-α; galectin; Proinflammatory cytokines; CFA; Inducible nitric oxide synthase; Antineoplastic agent; Endocrinopathy; Animal model; Multiple dose; Immunology; Gene; Genetics; Streptozotocin; Enzyme; Diabetes mellitus; Low dose; Rodentia; Cytokine; Inflammation; Interleukin 17; Nitric-oxide synthase; Vertebrata; Sensitivity; Mammalia; Mouse; Animal; Galectin 3; Oxidoreductases; Mutation; Gamma interferon
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2008.08.024

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.