Recombinant TsP53 modulates intestinal epithelial barrier integrity via upregulation of ZO-1 in LPS-induced septic mice

Abstract

Tight junctions (TJs) are a critical component in maintaining the intestinal mucosal barrier function and gastrointestinal health of animals. Gut barrier dysfunction contributes to the initiation and development of sepsis which induces an uncontrollable systemic inflammatory response and gives rise to life-threatening clinical conditions. Excretory-secretary antigens from Trichimella spiralis (T. spiralis) have been reported to protect from sepsis in a mouse model, however the mechanism remains to be elucidated. Mice were treated with recombinant T. spiralis 53-kDa glycoprotein (rTsP53) at 2 or 6 h following lipopolysaccharide (LPS) injection. Survival rate, serum systemic inflammation, Chiu's score, D-lactic acid (D-LA) and diamine oxidase (DAO) as intestinal injured biomarkers, bacterial translocation and growth in peritoneal fluid (PF) and mesenteric lymph nodes (MLN), intestinal tight junction structure and protein zona occludens (ZO)-l expression were investigated. In LPS-induced septic mice, rTsP53 was demonstrated to protract the survival and inhibit serum systemic inflammatory response, and then, allayed morphological alteration, decreased the release of D-LA and DAO from intestines. Furthermore, LPS-induced intestinal permeability, bacterial translocation and growth in PF, MLN and vital organs were significantly suppressed by rTsP53 treatment. Notably, rTsP53 treatment markedly improved the intestinal tight junction damaged in sepsis via promoting ZO-1 expression. These results demonstrated that rTsP53 ameliorated LPS-induced intestinal injury and is a potential protective agent for treatment of sepsis.