FoxO1 regulates TLR4/MyD88/MD2‐NF‐κB inflammatory signalling in mucosal barrier injury of inflammatory bowel disease

In this study, FoxO1 transgenic mice (transgenic, FoxO1‐Tg) and C57BL/6 wild‐type (wild‐type, FoxO1‐WT) mice were used to establish chronic colitis by drinking water containing dextran sulphate sodium (DSS). Afterwards, we observed the life changes in mice and assessed the pathological changes by H&E tissue staining. In addition, the TLR4/MyD88/MD2‐NF‐κB inflammatory signals were detected. As a result, under DSS treatment, the activation level of TLR4/MyD88/MD2‐NF‐κB inflammatory signal was higher in FoxO1‐Tg mice than that in FoxO1‐WT mice. Meanwhile, the intestinal mucosal tissue damage was more severe, the down‐regulation of tight junction protein level was more significant and the life quality was decreased to a higher degree in FoxO1‐Tg mice compared with those in FoxO1‐WT mice. Caco‐2 cells were used to mimic the intestinal mucosal barrier model for in vitro assays. In addition, lentiviral packaging FoxO1 overexpressing plasmid was transfected into Caco‐2 cells for FoxO1 overexpression. TNF‐α intervention was performed for intestinal mucosal inflammatory response model. Consequently, the down‐regulation of FoxO1 inhibited the activation of TLR4/MyD88/MD2‐NF‐κB inflammatory signal, decreased the mucosal barrier permeability and up‐regulated the expression of tight junction protein. By contrast, the overexpression of FoxO1 increased the mucosal barrier permeability and down‐regulated the level of tight junction protein.