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

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Abstract

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.

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Acknowledgments

This study was supported by Grant 12SJGGYY09 from the science research project of Songjiang District Science and Technology Committee of Shanghai (12SJGGYY09).

Conflict of interest

None.

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Author notes

    Authors and Affiliations

    1. Department of General Intensive Care Unit, Songjiang Hospital Affiliated to First People’s Hospital, Shanghai Jiao Tong University, No. 746, Zhongshan Road, Shanghai, 201600, China

      Guoguang Ma, Bin Shi, Jingquan Liu, Hongze Zhang, Zijun YinTao, Shengxia Wan & Wanhua Yang

    2. Department of Central Laboratory, Songjiang Hospital Affiliated to First People’s Hospital, Shanghai Jiao Tong University, Shanghai, 201600, China

      Xiaoli Lou, Dongyu Liang & Yanqiang Hou

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    1. Guoguang Ma
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    2. Bin Shi
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    3. Jingquan Liu
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    5. Zijun YinTao
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    10. Wanhua Yang
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    Corresponding author

    Correspondence to Bin Shi.

    Additional information

    Guoguang Ma and Bin Shi have contributed to the work equally and should be regarded as joint first authors.

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    Ma, G., Shi, B., Liu, J. et al. Nod2–Rip2 Signaling Contributes to Intestinal Injury Induced by Muramyl Dipeptide Via Oligopeptide Transporter in Rats. Dig Dis Sci 60, 3264–3270 (2015). https://doi.org/10.1007/s10620-015-3762-1

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    • DOI: https://doi.org/10.1007/s10620-015-3762-1

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