Exosomes derived from Hp-positive gastritis patients inhibit MCP-1 and MIP-1α expression in intestinal epithelial cells and improve DSS-induced colitis in mice

Abstract

Background: Previous studies have suggested that Helicobacter pylori (H. pylori, Hp) infection has a protective function in inflammatory bowel disease (IBD); Exosomes (Exo) are novel cell-cell communication mediators and their association with inflammatory immune responses has received great attention. however the mechanisms regarding the role of exosomes between Hp infection and IBD are limited.Methods: Human intestinal epithelial cells were treated with serum exosomes derived from Hp-positive chronic gastritis patients (Exo(Hp)), the expression of cytokines, inflammasome and signal pathway genes were detected by antibody microarray or PCR array. Furthermore, DSS-induced colitis mice were treated with exosomes by intraperitoneally injection to study the effect of Exo(Hp) in IBD.Results: Serum exosomes derived from Hp-positive chronic gastritis patients promoted NLRP12 expression in intestinal epithelial cells, and NLRP12 decreased chemokine MCP-1 and MIP-1α expression by inhibiting the Notch signaling pathway. In vivo, Exo(Hp) could attenuated inflammatory responses in DSS-induced colitis and improved colitis symptoms, which was associated with the increase in NLRP12 expression. Furthermore, the immunohistochemistry results showed that NLRP12 was negatively correlated with the disease activity of pediatric IBD patients. Conclusions: Exo(Hp) inhibited the Notch signaling pathway through the promotion of NLRP12 expression to further down-regulate MCP-1 and MIP-1α expression in intestinal epithelial cells and thereby attenuate DSS-induced colitis in mice. These results provide new theoretical bases for further elucidation of the intestinal protection mechanisms of Hp infection in IBD, and provide new targets for explorations of effective interventional strategies for IBD.