Nod2-Rip2 Signaling Contributes to Intestinal Injury Induced by Muramyl Dipeptide Via Oligopeptide Transporter in Rats

Dig Dis Sci. 2015 Nov;60(11):3264-70. doi: 10.1007/s10620-015-3762-1. Epub 2015 Jul 3.


Background and aims: PepT1 can transport bacterial oligopeptide products and induce intestinal inflammation. Our aim was to investigate the mechanism of the small intestine injury induced by bacterial oligopeptide product muramyl dipeptide (MDP) which is transported by PepT1.

Methods: We perfused the jejunum with a solution with or without MDP, or with a solution of MDP + Gly-Gly and explored the degree of inflammation to determine the role of PepT1-Nod2 signaling pathway in small intestine mucosa.

Results: MDP perfusion induced inflammatory cell accumulation and intestinal damage, accompanied by an increase in mucosal Nod2 and Rip2 transcript expression. NFκB activity and inflammatory cytokine expression, including serum levels of TNF-α, IL-1β, and IL-6, increased in the MDP group compared to the controls; these effects were reversed by perfusion of the nutritional dipeptide Gly-Gly.

Conclusion: MDP can be transported through PepT1, causing inflammatory damage in the rat small intestine. Nod2-Rip2-NFκB signaling involved in the small intestinal inflammatory injury caused by MDP which is transported through PepT1.

Keywords: Muramyl dipeptide (MDP); Nod signaling adaptor protein; PepT1 protein; Small intestine injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / metabolism
  • Acetylmuramyl-Alanyl-Isoglutamine / toxicity*
  • Animals
  • Cytokines / metabolism
  • Enteritis / chemically induced*
  • Enteritis / enzymology
  • Enteritis / pathology
  • Glycylglycine / pharmacology
  • Inflammation Mediators / metabolism
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / enzymology
  • Intestinal Mucosa / pathology
  • Jejunum / drug effects*
  • Jejunum / enzymology
  • Jejunum / pathology
  • Male
  • NF-kappa B / metabolism
  • Nod2 Signaling Adaptor Protein / metabolism*
  • Peptide Transporter 1
  • Rats, Sprague-Dawley
  • Receptor-Interacting Protein Serine-Threonine Kinase 2 / metabolism*
  • Signal Transduction / drug effects
  • Symporters / metabolism*


  • Cytokines
  • Inflammation Mediators
  • NF-kappa B
  • NOD2 protein, rat
  • Nod2 Signaling Adaptor Protein
  • Peptide Transporter 1
  • Slc15a1 protein, rat
  • Symporters
  • Glycylglycine
  • Acetylmuramyl-Alanyl-Isoglutamine
  • Receptor-Interacting Protein Serine-Threonine Kinase 2