E.coli JM83 Damages Mucosal Barrier Inducing Hirschsprung-Associated Enterocolitis via Activated TLR4 / NF-κB / P-p38 Signaling

Purpose Hirschsprung-associated enterocolitis (HAEC) is characterized by intestinal mucosal damage and unbalance of intestinal microbiota. Recent studies have shown that the TLR4/NF-κB/p-p38 signaling in the intestine is of great importance to intestinal mucosal integrity. This study aimed to investigate the role of TLR4/NF-κB/p-p38 signaling in the pathogenesis of HAEC in Escherichia coli (E. coli) JM83 infected Endothelin receptor B (Ednrb)−/− mice. Methods Ednrb −/− mice were administered with E. coli JM83 by oral gavage to establish the HAEC model, mice were randomly divided into WT group, Ednrb−/− group and Ednrb−/−+ E. coli JM83 group. The role of TLR4/NF-κB/p-p38 signaling was evaluated by vivo study. Results The activation of the TLR4/NF-κB/p-p38 signaling induced by E. coli JM83 caused HAEC in Ednrb−/− mice, which was evidenced by a significantly increased expression of TNF-α, TGF-β and IL-10, decreased density of F-actin protein. While TLR4 knockdown improved the degree of enterocolitis and attenuated the expression of IL-10, TNF-α, TGF-β and increased the density of F-actin protein in Ednrb−/− mice after E. coli infection. Conclusions These results indicate that E. coli JM83 activates TLR4/NF-κB/p-p38 signaling to promote the development of HAEC. However, inhibition of this signaling may be benefit to the treatment and prevention of HAEC.