Pharmacological Inhibition of Amyloidogenic APP Processing and Knock-Down of APP in Primary Human Macrophages Impairs the Secretion of Cytokines.

ABSTRACT: It has been previously shown that the amyloid precursor protein (APP) support the innate immune defense as an immune receptor. Amyloid β (Aβ) peptides seem to have properties of an antimicrobial peptide and can act as opsonines. In APP-deficient mouse models, a reduced secretion of cytokines has been observed. Still, it is unclear whether this can be attributed to the lack of APP or to the missing secretion of Aβ peptides. We inhibited the secretion of Aβ peptides in primary human monocyte derived macrophages with the γ-secretase inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine-t-butyl-ester (DAPT) or the β-secretase inhibitor GL-189. Alternatively, we knocked down APP by transfection with siRNA. We measured tumor necrosis factor α (TNFα), interleukin 6 (IL-6) and interleu

SUBMITTER: Spitzer P 

PROVIDER: S-EPMC7494750 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature