The Anti-Inflammatory Effects of the Dietary Dipeptide, Gamma-Glutamylvaline in a Mouse Model of LPS-Induced Sepsis

Abstract

This study endeavored to identify the anti-inflammatory activity and signaling mechanism of the bioactive dietary dipeptide gamma-L-glutamyl-L-valine (γ-EV) via calcium-sensing receptor (CaSR) activation in a lipopolysaccharide (LPS)-induced mouse model of sepsis. Sepsis occurs when the otherwise tightly-regulated immune and inflammatory response that eliminates invading pathogens and repairs injured tissues, switches to an uncontrolled response that causes an acute life-threatening inflammatory syndrome. γ-EV had anti-inflammatory activity in BALB/c mice with LPS-induced sepsis as measured by the reduction of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in plasma and small intestine tissue. There was a γ-EV-mediated decrease in the phosphorylation of the downstream signaling proteins JNK and IκBα in small intestine tissue, which indicates γ-EV likely has an effect on an upstream signaling protein common to both the AP-1 and NF-κB pathways. The study proposes that a direct interaction of CaSR-recruited β-arrestin2 with TRAF6, TAB1, and IκBα constitutes γ-EV’s anti-inflammatory activity in LPS-induced inflammation. This study provides evidence that γ-EV has health-promoting activity.