Background
The Highly Pathogenic Island (HPI) found in Yersinia pestis can be horizontally transferred to E. coli, enhancing its virulence and pathogenicity. Ubiquitin (Ub) acts as an activator of the NF-κB pathway and plays a critical role in the inflammatory response. However, the precise mechanism by which Ub and the regulated TLR4/NF-κB pathway contribute to HPI-induced intestinal inflammation in E. coli remains unclear.
Conclusions
In conclusion, this study sheds light on the significant role of the Ub-regulated TLR4/NF-κB pathway in E. coli HPI-induced duodenitis, offering novel insights into the pathogenesis of E. coli infections.
Results
In this study, we established Ub overexpression models of small intestinal epithelial cells (in vitro) and BALB/c mice (in vivo) and infected these models with HPI-rich E. coli. We investigated the role of the Ub-regulated TLR4/NF-κB pathway in E. coli HPI-induced intestinal inflammation through qPCR, ELISA, immunofluorescence, immunohistochemistry, and H&E staining. Our findings confirmed that E. coli HPI promoted the expression of Ub, TLR4, and NF-κB in IPEC-J2 cells and induced the translocation of NF-κB p65 protein to the nucleus. Further investigations revealed that Ub overexpression enhanced epithelial cell damage induced by E. coli HPI. This was accompanied by up-regulation of mRNA levels of TLR4, MyD88, NF-κB, IL-1β, and TNF-α, as well as increased release of the inflammatory factors IL-1β and TNF-α. In a mouse model with Ub overexpression infected with E. coli HPI, we observed that Ub overexpression promoted E. coli HPI-induced intestinal inflammation. Mechanistically, E. coli HPI induced intestinal epithelial cell damage by inducing Ub overexpression and modulating the TLR4/NF-κB pathway. Conclusions: In