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PR-39 Ameliorates Salmonella Typhimurium-induced Intestinal Epithelial Barrier Dysfunction
Salmonella enterica Serovar Typhimurium infection is a primary enteric pathogenic disease affecting both human and animals. PR-39 is a porcine antimicrobial peptide that shows strong antibacterial effects towards Salmonella Typhimurium in vitro and multiple immunomodulation functions. Here we investigated the potential mechanisms of PR-39 in preventing Salmonella typhimurium-induced gut barrier dysfunction in mouse infection model and in polarized intestinal porcine epithelial cell line IPEC-J2. The intestinal permeability, the expression of tight junction proteins, and the biodistribution of PR-39 was determined by ussing chamber, immunofluorescence and qRT-PCR, and in vivo fluorescence imaging technology, respectively. One-way ANOVAs were performed using a 95% confidence interval. The results revealed that PR-39 attenuated the altered ileum architecture, reduced the increased intestinal permeability in Salmonella infected mice. These protective effects were not attributed to the antibacterial activity of PR-39, because PR-39 showed no antimicrobial activity against Salmonella typhimurium in simulated intestinal liquids or serum. Moreover, pre-treatment with PR-39 significantly reduced the adhesion and invasion of Salmonella typhimurium toward polarized IPEC-J2 monolayer, and attenuated the decreased ZO-1 and claudin-1 expression caused by Salmonella infection. Collectively, these findings provide evidences that PR-39 could prevent the Salmonella typhimurium-induced intestinal epithelial barrier dysfunction through an antimicrobial-independent mechanism.
Keywords: Intestinal epithelial barrier function; PR-39; Salmonella Typhimurium;