title: The C5a complement activation peptide increases IL-1beta and IL-6 release from amyloid-beta primed human monocytes: implications for Alzheimer's disease.
abstract: Alzheimer's disease (AD) brains contain large numbers of amyloid-beta peptide (Abeta) deposits associated with activated microglia, astrocytes and dystrophic neurites. Activated complement components and pro-inflammatory cytokines are also present, indicative of focal inflammation. However, neither Abeta, nor the chemokine-like mediator, C5a, which is generated by Abeta-mediated complement activation, significantly activates microglia, as assessed by pro-inflammatory cytokine release. We evaluated the possibility that both together would co-stimulate such release using the THP-1 human monocytic cell line as a microglial surrogate, and found this to be the case. These studies support the hypothesis that Abeta and C5a induce a chronic microglia-mediated focal inflammatory response in AD.
authors.affiliation: College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: O'Barr
authors.forename: N R
authors.initials: NR
authors.lastname: Cooper
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000494:pharmacology*; D002460:Cell Line; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology; D015936:Complement C5a / Q000276:immunology / Q000494:pharmacology*; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D017628:Microglia / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D016229:Amyloid beta-Peptides; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D015936:Complement C5a