title: CXCL8 protects human neurons from amyloid-β-induced neurotoxicity: relevance to Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid-β (Aβ) deposition in senile plaques colocalized with activated microglia and astrocytes. Recent studies suggest that CXCL8 is involved in the AD pathogenesis. The objective of this study was to determine the cellular sources of CXCL8 in the central nervous system during AD pathogenesis, and investigate the effects of CXCL8 on neuronal survival and/or functions. Our results showed significantly higher CXCL8 levels in AD brain tissue lysates as compared to those of age-matched controls. Upon Aβ and/or pro-inflammatory cytokine stimulation, microglia, astrocytes and neurons were all capable of CXCL8 production in vitro. Although CXCL8-alone did not alter neuronal survival, it did inhibit Aβ-induced neuronal apoptosis and increased neuronal brain-derived neurotrophic factor (BDNF) production. We conclude that microglia, astrocytes and neurons, all contribute to the enhanced CXCL8 levels in the CNS upon Aβ and/or pro-inflammatory cytokine stimulation. Further, CXCL8 protects neurons possibly by paracrine or autocrine loop and regulates neuronal functions, therefore, may play a protective role in the AD pathogenesis.
authors.affiliation: Department of Cell Biology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.lastname: Ashutosh
authors.forename: Wei
authors.initials: W
authors.lastname: Kou
authors.forename: Robin
authors.initials: R
authors.lastname: Cotter
authors.forename: Kathleen
authors.initials: K
authors.lastname: Borgmann
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Raisa
authors.initials: R
authors.lastname: Persidsky
authors.forename: Namita
authors.initials: N
authors.lastname: Sakhuja
authors.forename: Anuja
authors.initials: A
authors.lastname: Ghorpade
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D016209:Interleukin-8; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)