Heparanase prevents the development of type 1 diabetes in non-obese diabetic mice by regulating T-cell activation and cytokines production.

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.

• Authors: Menachem Bitan, Lola Weiss, Michael Zeira, Shoshana Reich, Orit Pappo, Israel Vlodavsky, Shimon Slavin
• Journal: Diabetes/metabolism research and reviews (Diabetes Metab Res Rev) 2008 Jul-Aug Vol. 24 Issue 5 Pg. 413-21 ISSN: 1520-7552 [Print] England
• PMID: 18561210 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Interleukin-12
• Interleukin-4
• Interferon-gamma
• heparanase
• Glucuronidase

Topics

• Animals
• Cytokines (biosynthesis)
• Diabetes Mellitus, Type 1 (prevention & control)
• Female
• Glucuronidase (pharmacology)
• Humans
• Interferon-gamma (biosynthesis)
• Interleukin-10 (biosynthesis)
• Interleukin-12 (biosynthesis)
• Interleukin-4 (biosynthesis)
• Lymphocyte Activation (drug effects)
• Mice
• Mice, Inbred NOD
• Th1 Cells (physiology)
• Th2 Cells (physiology)
• Tumor Necrosis Factor-alpha