Mesenchymal stem cells inhibited the inflammation and oxidative stress in LPS-activated microglial cells through AMPK pathway

Abstract

Microglia are the resident mononuclear immune cells of the central nervous system (CNS) and the activation of microglia contributes to the production of excessive neurotoxic factors. In particular, the overproduction of neurotoxic factors has critical effects on the development of brain injuries and neurodegenerative diseases. The human bone marrow-derived mesenchymal stem cells (hBM-MSCs) have blossomed into an effective approach with great potential for the treatment of neurodegenerative diseases and gliomas. The present study aimed to investigate the mechanism behind the therapeutic effect of hBM-MSCs on the activation of microglia in vitro. Specifically, the hBM-MSCs significantly inhibited the proliferation of lipopolysaccharide-activated microglial cells (LPS)-activated microglial cells. Additionally, we investigated whether the adenosine-monophosphate-activated protein kinase signaling (AMPK) pathway was involved in this process. Our data demonstrated that hBM-MSCs significantly increased the phosphorylated AMPK in LPS-activated microglial cells. In addition, our study indicated the inhibitory effect of hBM-MSCs on the pro-inflammatory mediators and oxidative stress by the AMPK pathway in LPS-activated microglial cells. These results could shed light on the understanding of the molecular basis for the inhibition of hBM-MSCs on LPS-activated microglial cells and provide a molecular mechanism for the hBM-MSCs implication in brain injuries and neurodegenerative diseases.