Chondroitin sulfate disaccharide stimulates microglia to adopt a novel regulatory phenotype.
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 RT-PCR 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 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.
Ebert
Stefanie
S
Institute of Human Genetics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
Schoeberl
Tobias
T
Walczak
Yana
Y
Stoecker
Katharina
K
Stempfl
Thomas
T
Moehle
Christoph
C
Weber
Bernhard H F
BH
Langmann
Thomas
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism*; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000494:pharmacology*; D020869:Gene Expression Profiling; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis / Q000502:physiology; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D015415:Biomarkers; D011508:Chondroitin Sulfate Proteoglycans; D009569:Nitric Oxide; D007371:Interferon-gamma