title: Aging enhances release of exosomal cytokine mRNAs by Aβ1-42-stimulated macrophages.
abstract: Amyloid-β1-42 (Aβ) peptide effects on human models of central nervous system (CNS)-patrolling macrophages (Ms) and CD4 memory T-cells (CD4-Tms) were investigated to examine immune responses to Aβ in Alzheimer's disease. Aβ and lipopolysaccharide (LPS) elicited similar M cytokine and exosomal mRNA (ex-mRNA) responses. Aβ- and LPS-stimulated Ms from 20 ≥65-yr-old subjects generated significantly more IL-1, TNF-α, and IL-6, but not IL-8 or IL-12, and significantly more ex-mRNAs for IL-6, TNF-α, and IL-12, but not for IL-8 or IL-1, than Ms from 20 matched 21- to 45-yr-old subjects. CD4-Tm generation of IL-2, IL-4, and IFN-γ and, for young subjects, IL-10, but not IL-6, evoked by Aβ was significantly lower than with anti-T-cell antigen receptor antibodies (Abs). Abs significantly increased all CD4-Tm ex-mRNAs, but only IL-2 and IL-6 ex-mRNAs were increased by Aβ. There were no significant differences between cytokine and ex-mRNA responses of CD4-Tms from the old compared to the young subjects. M-derived serum exosomes from the old subjects had significantly higher IL-6 and IL-12 ex-mRNA levels than those from the young subjects, whereas there were no differences for CD4-Tm-derived serum exosomes. An Aβ level relevant to neurodegeneration elicited broad M cytokine and ex-mRNA responses that were significantly greater in the old subjects, but only narrow and age-independent CD4-Tm responses.
authors.affiliation: 3UCSF Geriatric Research Center, 1719 Broderick Street, San Francisco, CA 94115-2525, USA. E-mail edward.goetzl@ucsf.edu.
authors.forename: Masato
authors.initials: M
authors.lastname: Mitsuhashi
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Taub
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kapogiannis
authors.forename: Erez
authors.initials: E
authors.lastname: Eitan
authors.forename: Linda
authors.initials: L
authors.lastname: Zukley
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Janice B
authors.initials: JB
authors.lastname: Schwartz
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Goetzl
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D012333:RNA, Messenger; C075222:amyloid beta-protein (1-42)
keywords: T cells; dementia; immunosenescence; membrane vesicle; neural proteinopathy