title: Mutant SOD1 G93A microglia have an inflammatory phenotype and elevated production of MCP-1.
abstract: The inflammatory response in amyotrophic lateral sclerosis (ALS) is well documented but the underlying cellular mechanisms have not been fully elucidated. We report that microglia isolated from the mutant human superoxide dismutase 1 (SOD1) G93A transgenic mouse model of ALS have an increased response to the inflammatory stimulus, lipopolysaccharide. Cell surface area and F4/80 surface marker, both indicators of cell activation, are increased relative to transgenic wild-type human SOD1 microglia. Monocyte chemoattractant protein-1, known to be increased in ALS, is produced at three-fold higher levels by SOD1 G93A than by wild-type human SOD1 microglia, under activating conditions. This novel finding implicates ALS microglia as a source of the increased monocyte chemoattractant protein-1 levels detected in ALS patients and in the ALS mouse model.
authors.affiliation: Department of Neuroscience, School of Medicine and Biomedical Sciences, The University of Sheffield, UK.
authors.forename: Siranush A
authors.initials: SA
authors.lastname: Sargsyan
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Blackburn
authors.forename: Siân C
authors.initials: SC
authors.lastname: Barber
authors.forename: Peter N
authors.initials: PN
authors.lastname: Monk
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Shaw
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D015232:Dinoprostone