Heparanase prevents the development of type 1 diabetes in non-obese diabetic mice by regulating T-cell activation and cytokines production |
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Authors: | Bitan Menachem Weiss Lola Zeira Michael Reich Shoshana Pappo Orit Vlodavsky Israel Slavin Shimon |
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Institution: | Department of Bone Marrow Transplantation, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel. menachembi@tasmc.health.gov.il |
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Abstract: | BACKGROUND: Heparanase is an endo-beta-D-glucuronidase that cleaves heparan sulfate saccharide chains. The enzyme promotes cell adhesion, migration and invasion, and was shown to play a significant role in cancer metastasis and angiogenesis. METHODS: The present study focuses on the involvement of heparanase in autoimmunity, applying the murine non-obese diabetic (NOD) model, a T-cell-dependent disease often used to investigate the pathophysiology of type 1 diabetes. RESULTS: It was found that intra-peritoneal administration of heparanase ameliorated the clinical signs of the disease. In vitro studies revealed that heparanase has an inhibitory effect on the activation of T-cells through modulation of their repertoire of cytokines indicated by a marked increase in the levels of IL-4 and IL-10, and a parallel decrease in IL-12, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). CONCLUSIONS: We suggest that heparanase induces a shift from a Th1- to Th2-phenotype, resulting in inhibition of diabetes in NOD mice and possibly other autoimmune disorders. |
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Keywords: | heparanase non‐obese diabetes T‐cells activation cytokines |
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