Dendritic cell exosome‑shuttled miRNA146a regulates exosome‑induced endothelial cell inflammation by inhibiting IRAK‑1: A feedback control mechanism

Activation of endothelial cells is the first step of atherosclerosis. The current authors have previously reported that exosomes from mature dendritic cells (mDCexo) participate in endothelial inflammation and atherosclerosis through membrane tumor necrosis factoralpha mediated the nuclear factor (NF)kappaB signaling pathway. However, whether mDCexo shuttled microRNAs (miRNAs/miRs) play a role in endothelial inflammation remains unknown. In this study, mDCexo were cocultured with human umbilical vein endothelial cells (HUVECs) and the expression of adhesion molecules, such as vascular cell adhesion molecule1, intercellular adhesion molecule1 and ESelectin was investigated. Then the expression of miRNAs in DCexo was explored and the role of miR146a in endothelial inflammation was investigated. mDCexos were first demonstrated to increase endothelial expression of adhesion molecules through a quick activation of the NFkappaB signaling pathway. Then it was demonstrated that HUVECs resistant to a second stimulation after the first stimulation by mDCexo. A set of miRNAs were targeted and their expression in HUVECs stimulated with mDCexo was measured. Finally, it was confirmed that mDCexo shuttles miR146a into HUVECs and the shuttled miR146a contributes to protect HUVECs from a second stimulation through inhibiting interleukin1 receptorassociated kinase. These data suggest a negative feedback loop of inflammation regulation by DCexo.