期刊
DIABETES-METABOLISM RESEARCH AND REVIEWS
卷 24, 期 5, 页码 413-421出版社
WILEY
DOI: 10.1002/dmrr.868
关键词
heparanase; non-obese diabetes; T-cells activation; cytokines
资金
- Juvenile Diabetes Research [2006-695]
- Sigma-Tau Research Department, Pomezia, Rome, Italy [ST1514]
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, turnout 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. Copyright (C) 2008 John Wiley & Sons, Ltd.
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