title: Pro-inflammatory cytokines reduce the proliferation of NG2 cells and increase shedding of NG2 in vivo and in vitro.
abstract: Neuron glial 2 (NG2) cells become strongly activated in injured brain areas. The activation is characterized by increased proliferation as well as increased expression and shedding of the proteoglycan NG2 expressed on their cell surface. It is currently not known how these cells respond to low-grade neuroinflammation provoked by systemic inflammation. To investigate this, we analyzed NG2 cell proliferation as well as soluble NG2 (sNG2) in cerebrospinal fluid (CSF) from rats treated with an acute intraperitoneal (i.p) injection of lipopolysaccharides (LPS) or saline and sacrificed after 2 or 24 hours. The systemically induced neuroinflammation was confirmed as elevated levels of cytokines, including interleukin (IL)-6 and IL-1β, and MHCII expressing microglia were found 24 h after LPS treatment. At this time point NG2 cell proliferation was significantly decreased in both amygdala and hippocampus and sNG2 levels in CSF were increased twofold. We also exposed human NG2 cells in culture to IL-6 and IL-1β for 24 h and found, in line with our in vivo study, a direct impact of these cytokines reducing cell proliferation and increasing shedding of NG2. We conclude that LPS induced systemic inflammation significantly affects NG2 cell proliferation and shedding and that these two events at least in in part are mediated by IL-6 and IL-1β.
authors.affiliation: Lund University, Department of Clinical Sciences, Clinical Memory Research Unit, Wallenberg Laboratory, Malmö, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Wennström
authors.affiliation: Lund University, Department of Clinical Sciences, Clinical Memory Research Unit, Wallenberg Laboratory, Malmö, Sweden.
authors.forename: Shorena
authors.initials: S
authors.lastname: Janelidze
authors.affiliation: Aarhus University, Department of Clinical Medicine, Translational Neuropsychiatry Unit, Risskov, Denmark.
authors.forename: Cecilie
authors.initials: C
authors.lastname: Bay-Richter
authors.affiliation: Lund University, Department of Clinical Sciences, Clinical Memory Research Unit, Wallenberg Laboratory, Malmö, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.affiliation: Michigan State University, College of Human Medicine, Department of Psychiatry and Behavioral Medicine, Grand Rapids, Michigan, United States of America; Van Andel Research Institute, Laboratory of Behavioral Medicine, Grand Rapids, Michigan, United States of America.
authors.forename: Lena
authors.initials: L
authors.lastname: Brundin
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects* / Q000473:pathology*; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides