HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print June 12, 2008

This Article Full Text (Reprint (PDF)) Supplemental Tables 1 and 2 All Versions of this Article: jlb.0208138v1 84/3/736    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ebert, S. Articles by Langmann, T. PubMed PubMed Citation Articles by Ebert, S. Articles by Langmann, T.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0208138

Received for publication February 26, 2008.
Revised April 22, 2008.
Accepted for publication May 15, 2008.

Article

Chondroitin sulfate disaccharide stimulates microglia to adopt a novel regulatory phenotype

Stefanie Ebert ^*, Tobias Schoeberl ^*, Yana Walczak ^*, Katharina Stoecker ^*, Thomas Stempfl , Christoph Moehle , Bernhard H. F. Weber ^*, and Thomas Langmann ^*@

*Institute of Human Genetics, University of Regensburg, Regensburg, Germany; and Center for Fluorescent Bioanalysis, Regensburg, Germany

^@ To whom correspondence should be addressed. E-mail: thomas.langmann{at}klinik.uni-regensburg.de.

	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--stimulated primary microglia using real-time quantitative RT-PCR validation. Importantly, a unique transcriptional phenotype with anti-inflammatory and IFN- 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--induced apoptosis. Taken together, our data provide a unique transcript dataset 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.

Key Words: CSPG-DS • qRT-PCR • IFN- • nitric oxide