Research
Heparan sulfate proteoglycan induces the production of NO and TNF-α by murine microglia
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* Corresponding author: Pierluigi Baron pierluigi.baron@unimi.it
1 Department of Neurological Sciences, Centre for Excellence on Neurodegenerative Diseases and "Dino Ferrari" Center, University of Milan, Fondazione IRCCS "Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena", Via F. Sforza 35, 20122 Milan, Italy
2 Dept. Preclinical Sciences, University of Milano, 20157 - Milano and E.Medea Scientific Institute 23842 - Bosisio Pasini, Italy
Immunity & Ageing 2005, 2:11 doi:10.1186/1742-4933-2-11
Published: 16 July 2005Abstract
Background
A common feature of Alzheimer's disease (AD) pathology is the abundance of activated microglia in neuritic plaques containing amyloid-beta protein (Aβ) and associated molecules including heparan sulfate proteoglycan (HSPG). Besides the role as pathological chaperone favouring amyloidogenesis, little is known about whether or not HSPG can induce microglial activation. Cultures of primary murine microglia were used to assess the effect of HSPG on production of proinflammatory molecules that are known to be present in neuritic plaques of AD.
Results
HSPG stimulated up-regulation of tumor necrosis factor-alpha (TNF-α), production of inducible nitric oxide synthase (iNOS) mRNA and accumulation of TNF-α protein and nitrite (NO2-) in a time- and concentration-dependent manner. The effects of HSPG were primarily due to the property of the protein core as indicated by the lack of microglial accumulation of TNF-α and NO2- in response to denaturated HSPG or heparan sulfate GAG chains (HS).
Conclusion
These data demonstrate that HSPG may contribute to chronic microglial activation and neurodegeneration seen in neuritic plaques of AD.