Extracellular Vesicles Secreted by the Activated THP-1 Cells Influence the Inflammation Gene Expression in Zebrafish

Abstract—Extracellular vesicles secreted by immune cells may play a significant role in the initiation, maintenance, and progression of systemic inflammation. The aim of the study was to investigate the regulatory effect of extracellular vesicles (EVs) produced by activated monocyte-like THP-1 cells on expression levels of inflammatory genes in a zebrafish. Real-time PCR analysis was performed to investigate the relative expression levels of il-1β, il-6, tnf-α, ifn-γ, mpeg-1.1, mpeg-1.2, mpx, and il-10 genes in the brain, liver, and heart of zebrafish followed by intracelomic injection of EVs produced by THP-1 cells activated with tumor necrosis factor (TNF) and phorbol-12-myristate-13-acetate (PMA) at different concentrations. EVs, secreted by THP-1 cells activated with TNF at a concentration of 10 ng/mL and PMA at concentrations of 16 and 50 ng/mL, reduced the expression levels of il-1β, ifn-γ, tnf-α, mpx, mpeg-1.1, mpeg-1.2, and il-10 genes in the brain, heart and liver of Danio rerio. EVs secreted by THP-1 cells treated with TNF at doses of 10 and 20 ng/mL had opposite effects on the gene expression levels of il-1β in the brain, il-1β, il-10, and il-6 in the heart; on il-1β, il-10, mpx, and mpeg-1.2 in the liver. EVs secreted by THP-1 cells treated with PMA at doses of 16 and 50 ng/mL had opposite effects on the expression levels of il-6 and il-10 genes in the heart and ifn-γ gene in the liver. EVs produced by activated THP-1 cells have a systemic effect on Danio rerio manifested as changes in the expression of pro- and anti-inflammatory cytokine genes in the brain, liver, and heart. The qualitative composition of the EVs produced by activated THP-1 cells varies depending on the type and dose of the used stimulus, which reflects on strength and direction of the effects detected in vivo.