Secretome from SH-SY5Y APPSwe cells trigger time-dependent CHME3 microglia activation phenotypes, ultimately leading to miR-21 exosome shuttling.

In this study, we demonstrate that SH-SY5Y cells transfected with the Swedish mutant of APP695 (SHSwe) remarkably express increased inflammatory markers, combined with higher APP and Aβ1-40 production, when compared to naïve SH-SY5Y (SH) cells. Although exerting an early clearance effect on extracellular APP and Aβ accumulation when in co-culture with SHSwe cells, human CHME3 microglia gradually lose such property, and express both pro-inflammatory (iNOS, IL-1, TNF-α, MHC class II, IL-6) and pro-resolving genes (IL-10 and Arginase 1), while also evidence increased senescence-associated β-galactosidase activity. Interestingly, upregulation of inflammatory-associated miRNA (miR)-155, miR-146a and miR-124 b y SHSwe secretome was shown to be time-dependent and to inversely correlate with their respective targets (SOCS1, IRAK1 and C/EBPα). We report that microglia also internalize exosomes released from SHSwe cells, which are enriched in miR-155, miR-1464a, miR-124, miR-21 and miR-125 b and recapitulate the cells of origin. Furthermore, we show that SHSwe-derived exosomes are capable of inducing acute and delayed microglial upregulation of TNF-α, HMGB1 and S100B pro-inflammatory markers, from which only S100B is found on their derived exosomes. Most importantly, our data reveal that miR-21 is a consistent biomarker that is found not only in SHSwe cells and in released exosomes, but also in the recipient CHME3 microglia and their exosomes. This work contributes to the ...
Source: Biochimie - Category: Biochemistry Authors: Tags: Biochimie Source Type: research