Effect Of Nod2-Rip2Signaling Pathway On PepT1-mediated MDP Transport Induces Intestinal Inflammation

Objective:To explore the effect of Nod2-Rip2signaling pathway on the PepT1-mediated MDP transport induces intestinal inflammation.Methods:SD rats (n=80) were randomly divided into normal group, the experimental control group, MDP perfusion group and PepT1competitive inhibition group. Normal group without any treatment, the remaining three groups received intestinal perfusion. MDP or vehicle was added to the Krebs-Ringer buffer and perfused for at least4h. For the competition studies, Gly-Gly was added to the buffer before addition of MDP. The expression of Nod2and Rip2mRNA, the activation state of nuclear factor kappa B (NF-κB), the production of cytokines [tumor necrosis alpha (TNF-α), interleukin-8(IL-8)], and myeloperoxidase (MPO) activity, and histological analysis were determined in gut. The production of cytokines (TNFα, IL-1β) in blood serum were detected.Results:Nod2and Rip2mRNA were constitutively expressed in gut, and MDP elicited a robust activation of NF-κB and induced significant production of the different cytokines evaluated. Plasma TNFa, IL-1β disclosed a peak. These performance can be inhibited by Gly-Gly significantly.Conclusion:This report showed the implication of a membrane transporter (PepTl) in intestinal inflammation. PepTl-mediated transport of MDP and the Nod2-Rip2signaling pathway might play an important role in this inflammation.