Abstract
The aim of the work was to investigate accumulation of endogenous Aβ40 and cytokines (IL-1β, TNFα, IL-6, IL-10) in mononuclear cells and their secretion into incubation medium under Aβ42-aggregates’ toxicity and anti-inflammatory effects of curcumin. Mononuclear cells were isolated in Ficoll-Urografin density gradient from venous blood of healthy donors, resuspended and used for testing of homoaggregates of Aβ42 (15 nM), curcumin (54 pM) and their combinations on various timescales (0, 1, 2, 3, 6 and 24 hours). Endogenous Aβ40 and cytokines were detected in mononuclear cells and (separately) in incubation medium by ELISA. We demonstrated for the first time that homoaggregates of Aβ42 cause rapid accumulation of endogenous Aβ40 in mononuclear cells and accelerate its secretion into incubation medium. We found increased concentration of TNFα after 3 hours of incubation, and no changes in IL-1β concentration due to secretion of these pro-inflammatory factors into incubation medium. The concentrations of IL-6 in mononuclear cells were increased under effects of Aβ42 homoaggregates, and it was being secreted profoundly into incubation medium. Aβ42 did not affect IL-10 secretion, yet caused an increase in its intracellular concentration after 1 hour of incubation, which was subsequently suppressed. Curcumin prevented the increase in Aβ40 concentration in mononuclear cells and significantly decreased its secretion resulting from Aβ42 toxicity. Curcumin negated the activating effect of Aβ42 on pro-inflammatory cytokines, starting immediately for IL-1β and on 3-6 hours for TNFα, which resulted in decreased extracellular concentrations of these cytokines. The polyphenol also potentiated replenishing of intracellular IL-6 and IL-10 concentrations and their secretion into incubation medium.
Highlights
Alzheimer’s disease is the primary cause of senile dementia associated with amyloid-β peptides (Aβ), oligomers and aggregates of which exert toxic and destructive effects upon neural tissue [1,2,3,4,5]
One of the aims of the present work was to establish the possibility of secretion of Aβ40 produced by peripheral mononuclear cells into surrounding medium, which could be used as its indicator in biological fluids of patients with Alzheimer disease and of its function other than being an amyloidohenesis
It was sensible to investigate the effect of curcumin on accumulation and secretion of endogenous Aβ40 and cytokines by mononuclear cells of human peripheral blood in vitro under Аβ42 aggregates’ toxicity
Summary
Alzheimer’s disease is the primary cause of senile dementia associated with amyloid-β peptides (Aβ), oligomers and aggregates of which exert toxic and destructive effects upon neural tissue [1,2,3,4,5]. One of the aims of the present work was to establish the possibility of secretion of Aβ40 produced by peripheral mononuclear cells into surrounding medium, which could be used as its indicator in biological fluids of patients with Alzheimer disease and of its function other than being an amyloidohenesis. Another standing problem is finding approaches to eliminate causes for AβPP overexpression and amyloidogenic processing, and inhibiting the inflammation resulting from Aβ-aggregate toxici ty. It was sensible to investigate the effect of curcumin on accumulation and secretion of endogenous Aβ40 and cytokines by mononuclear cells of human peripheral blood in vitro under Аβ42 aggregates’ toxicity
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