Chondroitin sulfate disaccharide stimulates microglia to adopt a novel regulatory phenotype

Ebert, Stefanie and Schoeberl, Tobias and Walczak, Yana and Stoecker, Katharina and Stempfl, Thomas and Moehle, Christoph and Weber, Bernhard H. F. and Langmann, Thomas (2008) Chondroitin sulfate disaccharide stimulates microglia to adopt a novel regulatory phenotype. JOURNAL OF LEUKOCYTE BIOLOGY, 84 (3). pp. 736-740. ISSN 0741-5400, 1938-3673

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Abstract

A disaccharide degradation product of chondrotin sulfate proteoglycan-disaccharide (CSPG-DS) has been implicated previously in the inhibition of neurodegeneration by influencing microglia activation. In this study, genome-wide microarray analysis was used to identify specific gene expression profiles of CSPG-DS-stimulated BV-2 microglia-like cells. Gene products involved in phagocytosis, detoxification, migration, immune regulation, and antigen presentation were found to be altered significantly. These findings were replicated and compared with IFN-gamma-stimulated primary microglia using real-time quantitative RTPCR validation. Importantly, a unique transcriptional phenotype with anti-inflammatory and IFN-gamma counter-regulatory properties partially related to alternatively activated macrophages was identified. Using functional cell assays, we found that CSPG-DS-stimulated microglia possess increased phagocytic capacity but lack direct cytotoxic effects such as secretion of NO. Furthermore, conditioned media from CSPG-DS-treated microglia did not diminish the viability or cause apoptosis of cultured photoreceptor cells and partially rescued these cells from IFN-gamma-induced apoptosis. Taken together, our data provide a unique transcript data-set and important in vitro findings about the functional properties of CSPG-DS-activated microglia. These might be starting points to explore the in vivo role of CSPG-DS as a bioactive microglia regulator and its potential, therapeutic application in immune-related, neurodegenerative disorders.

Item Type: Article
Uncontrolled Keywords: CELLS; EXPRESSION; MIGRATION; ACTIVATION; POLARIZATION; MACROPHAGES; PROTECTS; RATS; neurodegeneration; microglia activation; neuroprotection; proteoglycans
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Humangenetik
Depositing User: Dr. Gernot Deinzer
Date Deposited: 26 Oct 2020 09:26
Last Modified: 26 Oct 2020 09:26
URI: https://pred.uni-regensburg.de/id/eprint/30393

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