Aging enhances release of exosomal cytokine mRNAs by Aβ1‐42‐stimulated macrophages. Issue 12 (6th September 2013)

• Record Type: Journal Article
• Authors: Mitsuhashi, Masato; Taub, Dennis D.; Kapogiannis, Dimitrios; Eitan, Erez; Zukley, Linda; Mattson, Mark P.; Ferrucci, Luigi; Schwartz, Janice B.; Goetzl, Edward J.
• Is Part Of: FASEB journal. Volume 27:Issue 12(2013)
• Page Start: 5141
• Page End: 5150
• Publication Date: 2013-09-06
• Subjects: membrane vesicle -- T cells -- immunosenescence -- neural proteinopathy -- dementia; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.13-238980
• Languages: English
• ISSNs: 0892-6638

Abstract

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 IL6 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.—Mitsuhashi, M., Taub, D. D., Kapogiannis, D., Eitan, E., Zukley, L., Mattson, M. P., Ferrucci, L., Schwartz, J. B., Goetzl, E. J., Aging enhances release of exosomal cytokine mRNAs by Aβ1‐42‐stimulated macrophages. FASEB J. 27, 5141–5150 (2013). www.fasebj.org