Heparanase prevents the development of type 1 diabetes in non‐obese diabetic mice by regulating T‐cell activation and cytokines production
M Bitan, L Weiss, M Zeira, S Reich… - Diabetes/metabolism …, 2008 - Wiley Online Library
M Bitan, L Weiss, M Zeira, S Reich, O Pappo, I Vlodavsky, S Slavin
Diabetes/metabolism research and reviews, 2008•Wiley Online LibraryBackground Heparanase is an endo‐β‐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 …
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 …
Background
Heparanase is an endo‐β‐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‐α) and interferon‐gamma (IFN‐γ).
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 © 2008 John Wiley & Sons, Ltd.
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