Open AccessDietary γ-Glutamyl Valine Ameliorates TNF-α-Induced Vascular Inflammation via Endothelial Calcium-Sensing Receptors
Author(s) -
Snigdha Guha,
Catherine J. Paul,
Sophie Alvarez,
Yoshinori Mine,
Kaustav Majumder
Publication year - 2020
Publication title -
journal of agricultural and food chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.203
H-Index - 297
eISSN - 1520-5118
pISSN - 0021-8561
DOI - 10.1021/acs.jafc.0c04526
Subject(s) - chemistry , inflammation , receptor , chemokine , tumor necrosis factor alpha , endocrinology , calcium sensing receptor , downregulation and upregulation , medicine , nitric oxide , calcium , biochemistry , calcium metabolism , gene , organic chemistry
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 ( P app ) of the peptide was found to be 1.56 × 10 -6 cm/s.