Dietary γ-Glutamyl Valine Ameliorates TNF-α-Induced Vascular Inflammation via Endothelial Calcium-Sensing Receptors

Snigdha Guha, Catherine Paul, Sophie Alvarez, Yoshinori Mine, Kaustav Majumder

Research output: Contribution to journalArticlepeer-review

Abstract

γ-Glutamyl valine (γ-EV), commonly found in edible beans, was shown to reduce gastrointestinal inflammation via activation of calcium-sensing receptors (CaSRs). The present study aimed to evaluate the efficacy of γ-EV in modulating the tumor necrosis factor-α-induced inflammatory responses in endothelial cells (ECs) via CaSR-mediated pathways. Human aortic ECs (HAoECs) were pretreated (2 h) with γ-EV (0.01, 0.1, and 1 mM). 1 mM pretreatment of γ-EV significantly reduced the upregulation of inflammatory adhesion molecules, VCAM-1 and E-selectin, by 44.56 and 57.41%, respectively. The production of cytokines IL-8 and IL-6 was significantly reduced by 40 and 51%, respectively, with 1 mM pretreatment of γ-EV. Similarly, there was a significant reduction in chemokine MCP-1 from a positive control of 9.70 ± 0.52 to 6.6 ± 0.43 ng/mL, after γ-EV treatment. The anti-inflammatory effect of γ-EV was attenuated by the treatment of the CaSR-specific inhibitor, NPS-2143, suggesting the involvement of CaSR-mediated pathways. Further studies identified the critical role of key modulators, such as β-arrestin2 and cyclic adenosine monophosphate response element-binding protein, in mediating the CaSR-dependent anti-inflammatory effect of γ-EV. Finally, the transport efficiency of γ-EV was evaluated through a monolayer of intestinal epithelial cells (Caco-2), and the apparent permeability (Papp) of the peptide was found to be 1.56 × 10-6 cm/s.

Original languageEnglish (US)
Pages (from-to)9139-9149
Number of pages11
JournalJournal of Agricultural and Food Chemistry
Volume68
Issue number34
DOIs
StatePublished - Aug 26 2020

Keywords

  • anti-inflammation
  • calcium-sensing receptor
  • endothelial cells
  • vascular inflammation
  • γ-glutamyl peptides

ASJC Scopus subject areas

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

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