E. coli JM83 damages the mucosal barrier in Ednrb knockout mice to promote the development of Hirschsprung-associated enterocolitis via activation of TLR4/p-p38/NF-κB signaling

Hirschsprung-associated enterocolitis (HAEC) is characterized by intestinal mucosal damage and an imbalance in the intestinal microbiota. Recent studies have indicated that the TLR4/p-p38/NF-kappa B signaling pathway in the intestine is of great importance to intestinal mucosal integrity. The present study aimed to investigate the role of TLR4/phosphorylated (p-)38/NF-kappa B signaling in the pathogenesis of HAEC in E. coli JM83-infected endothelin receptor B (Ednrb)(-/-) mice. Ednrb(-/-) mice were infected with E. coli JM83 by oral gavage to establish the HAEC model. Wild-type and Ednrb(-/-) mice were randomly divided into uninfected and E. coli groups. The role of TLR4/p-p38/NF-kappa B signaling was further evaluated by in vivo and in vitro analyses. The activation of the TLR4/p-p38/NF-kappa B signaling pathway induced by E. coli JM83 resulted in HAEC in Ednrb(-/-) mice, which was evidenced by a significant increase in the expression of TNF-alpha, TGF-beta and IL-10, and a decreased density of F-actin protein expression. TLR4 knockdown reduced the severity of enterocolitis and attenuated the expression of IL-10, TNF-alpha and TGF-beta, whilst increasing the density of F-actin protein in Ednrb(-/-) mice after E. coli infection. These results indicated that E. coli JM83 activates TLR4/p-p38/NF-kappa B signaling in Ednrb(-/-) to promote the development of HAEC. Thus, inhibition of this signaling pathway may benefit the treatment and prevention of HAEC.

Automated summary

This study found that the TLR4/p-p38/NF-kappa B signaling pathway plays a role in promoting the development of HAEC in Ednrb(-/-) mice under E. coli infection.