Autophagy induced by enterovirus 71 regulates the production of IL-6 through the p38MAPK and ERK signaling pathways

Abstract

Enterovirus 71 (EV71) is the main causative agent of hand, foot, and mouth disease (HFMD), which has high morbidity and mortality. It mainly threatens children under six years of age. Because of a poor understanding of its pathogenesis, there are no effective drugs to control EV71 infection. Previous studies showed that EV71 infection induced autophagy and the production of cytokine IL-6. However, the underlying mechanisms between autophagy and the production of IL-6 induced by EV71 remain unclear. This study aimed to reveal the regulatory mechanisms between autophagy and the expression of IL-6 induced by EV71 infection. Our results showed that the proliferation of human gastric epithelial (GES-1) cells was inhibited by EV71 in a time- and dose-dependent manner. In addition, EV71 induced autophagy in GES-1 cells. EV71 infection promoted the expression and the release of IL-6 to the extracellular space, although the expression and release were inhibited by autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) in GES-1 cells. The phosphorylated levels of p38MAPK and ERK proteins in GES-1 cells also increased after infection with EV71, and these changes were also reversed by 3-MA and CQ treatment. Our findings suggested that EV71-induced autophagy regulated the production of IL-6 through the p38MAPK and ERK signaling pathways.