Effect of β-amyloid peptide 42 on the dynamics of expression and formation of Аβ40, IL -1β, TNF α, IL -6, IL -10 by peripheral blood mononuclear cells in vitro and its correction by curcumin.

The toxic effect of Аβ-oligomers accompanies chronic inflammation, with cytokines as main mediators. Therefore, the cytokine link of inflammation becomes a new target on the way to restrain amyloidosis. The aim of the study was the effect of aggregated Аβ42 on the dynamics of expression and formation of endogenous Аβ40 and cytokines (IL-1β, TNFα, IL-6, IL-10) by peripheral blood mononuclear cells in vitro and its correction by curcumin. A suspension of mononuclear cells isolated ex tempore using ficoll-urografin gradient from venous blood samples of healthy volunteers were used to study the effects of Аβ42 (15 nM), curcumin (54 pM), and their combined action (at similar concentrations) in time dynamics: 0, 1, 3, 6 and 24 h incubation at 37 °C. Polymerase chain reaction with appropriate primers was used to determine the relative expression of mRNA for AβPP, TNFα, IL-1β, IL-6, IL-10 and enzyme-linked immunosorbent assay – to determine the content of Аβ40 and cytokines in mononuclear suspension during all periods of incubation. The individual dynamics AβPP and cytokine expression was shown under the action of the Aβ42, which had influence on the content of Aβ40, TNFα, IL-1β, IL-6 and IL-10 in mononuclear suspension. Curcumin displayed the inhibitory effect on gene expression of AβPP, TNFα and IL6, which resulted in the decrease of the level of these two cytokines and Aβ40. Thus, the dynamics of anti-inflammatory effect of curcumin in vitro for transcriptional and translational levels of cytokine’s formation by mononuclear cells was shown in the work. Direct inhibitory effect of curcumin on the concentration of endogenous Aβ40 during the 24 h incubation in conditions of toxic action of Aβ42 aggregates was established.