Intervention of Dietary Dipeptide Gamma-l-Glutamyl-l-Valine (γ-EV) Ameliorates Inflammatory Response in a Mouse Model of LPS-Induced Sepsis

Mackenzie E. Chee, Kaustav Majumder, Yoshinori Mine

Research output: Contribution to journalArticle

8 Scopus citations


Sepsis, the systemic inflammatory response syndrome (SIRS) with infection is one of the leading causes of death in critically ill patients in the developed world due to the lack of effective antisepsis treatments. This study examined the efficacy of dietary dipeptide gamma-l-glutamyl-l-valine (γ-EV), which was characterized previously as an anti-inflammatory peptide, in an LPS-induced mouse model of sepsis. BALB/c mice were administered γ-EV via oral gavage followed by an intraperitoneal injection of LPS to induce sepsis. The γ-EV exhibited antisepsis activity by reducing the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in plasma and small intestine. γ-EV also reduced the phosphorylation of the signaling proteins JNK and IκBα. We concluded that γ-EV could possess an antisepsis effect against bacterial infection in intestine. This study proposes a signaling mechanism whereby the calcium-sensing receptor (CaSR) allosterically activated by γ-EV stimulates the interaction of β-arrestin2 with the TIR(TLR/IL-1R) signaling proteins TRAF6, TAB1, and IκBα to suppress inflammatory signaling.

Original languageEnglish (US)
Pages (from-to)5953-5960
Number of pages8
JournalJournal of Agricultural and Food Chemistry
Issue number29
Publication statusPublished - Jul 26 2017



  • CaSR
  • LPS
  • TLR4
  • bioactive peptide
  • gamma-glutamyl peptides
  • sepsis

ASJC Scopus subject areas

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

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