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The pathways and mechanisms of muramyl dipeptide transcellular transport mediated by PepT1 in enterogenous infection

Guo-Guang Ma1, Bin Shi2, Xue-Peng Zhang1

  • 1Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Annals of Translational Medicine
|November 9, 2019
PubMed
Abstract

Insights

Muramyl dipeptide (MDP) transport via peptide transporter 1 (PepT1) activates intestinal inflammation. Inhibiting PepT1 with Gly-Gly blocks MDP

Area of Science:

  • Gastroenterology
  • Immunology
  • Molecular Biology

Background:

  • Transcellular transport of muramyl dipeptide (MDP) by peptide transporter 1 (PepT1) in intestinal epithelial cells (IECs) is crucial but not fully understood.
  • Investigating MDP transport mechanisms is vital for understanding enterogenous infections.

Purpose of the Study:

  • To elucidate the pathways and mechanisms of MDP transcellular transport in IECs during enterogenous infection.
  • To determine the role of PepT1 in MDP-induced intestinal inflammation and immune cell activation.

Main Methods:

  • Rats were divided into sham, MDP, and MDP + Gly-Gly groups to assess survival and intestinal changes.
  • Cytokine levels (IL-6, IL-1b, IL-8, IL-10, TNF-α, NO) were measured via ELISA.
  • NFκB inhibition and flow cytometry were used to analyze macrophage activation and dendritic cell antigen presentation.

Main Results:

  • MDP administration caused mortality, weight loss, and intestinal damage, which were ameliorated by Gly-Gly inhibition of PepT1.
  • PepT1 inhibition reduced MDP-induced inflammatory cytokines in serum and intestinal tissues.
  • MDP transport via PepT1 promotes macrophage activation and dendritic cell antigen presentation.

Conclusions:

  • The peptide transporter 1 (PepT1)-NFκB signaling pathway is critical for initiating intestinal inflammatory responses.
  • PepT1-mediated MDP transport plays a key role in the pathogenesis of intestinal inflammation.
Keywords:
Muramyl dipeptide (MDP)PepT1enterogenous infectionimmune cells

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