Inflammatory repertoire of Alzheimer's disease and nondemented elderly microglia in vitro.
We have previously developed and characterized isolated microglia and astrocyte cultures from rapid (<4 h) brain autopsies of Alzheimer's disease (AD) and nondemented elderly control (ND) patients. In the present study, we evaluate the inflammatory repertoire of AD and ND microglia cultured from white matter (corpus callosum) and gray matter (superior frontal gyrus) with respect to three major proinflammatory cytokines, three chemokines, a classical pathway complement component, a scavenger cell growth factor, and a reactive nitrogen intermediate. Significant, dose-dependent increases in the production of pro-interleukin-1beta (pro-IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory peptide-1alpha (MIP-1alpha), IL-8, and macrophage colony-stimulating factor (M-CSF) were observed after exposure to pre-aggregated amyloid beta peptide (1-42) (Abeta1-42). Across constitutive and Abeta-stimulated conditions, secretion of complement component C1q, a reactive nitrogen intermediate, and M-CSF was significantly higher in AD compared with ND microglia. Taken together with previous in situ hybridization findings, these results demonstrate unequivocally that elderly human microglia provide a brain endogenous source for a wide range of inflammatory mediators.
Lue
L F
LF
Sun Health Research Institute, Sun City, Arizona 85372, USA.
Rydel
R
R
Brigham
E F
EF
Yang
L B
LB
Hampel
H
H
Murphy
G M
GM
Brachova
L
L
Yan
S D
SD
Walker
D G
DG
Shen
Y
Y
Rogers
J
J
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis; D015922:Complement C1q / Q000096:biosynthesis / Q000187:drug effects; D003337:Corpus Callosum / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005625:Frontal Lobe / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D009573:Nitrites; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D015922:Complement C1q