Effect of curcumin on accumulation in mononuclear cells and secretion in incubation medium of Аβ(40) and cytokines under local excess of Аβ(42)-homoaggregates

摘要

The aim of the work was to investigate accumulation of endogenous Aβsub40/sub and cytokines (IL-1β, TNFα, IL-6, IL-10) in mononuclear cells and their secretion into incubation medium under Aβsub42/sub-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 Aβsub42/sub (15 nM), curcumin (54 pM) and their combinations on various timescales (0, 1, 2, 3, 6 and 24 hours). Endogenous Aβsub40/sub and cytokines were detected in mononuclear cells and (separately) in incubation medium by ELISA. We demonstrated for the first time that homoaggregates of Aβsub42/sub cause rapid accumulation of endogenous Aβsub40/sub 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 Aβsub42/sub homoaggregates, and it was being secreted profoundly into incubation medium. Aβsub42/sub 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 Aβsub40/sub concentration in mononuclear cells and significantly decreased its secretion resulting from Aβsub42/sub toxicity. Curcumin negated the activating effect of Aβsub42/sub 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.