Glycine is a competitive antagonist of the TNF receptor mediating the expression of inflammatory cytokines in 3T3-L1 adipocytes

Inflamm Res. 2021 May;70(5):605-618. doi: 10.1007/s00011-021-01462-1. Epub 2021 Apr 20.

Abstract

Objective: To determine the involvement of TNF-α and glycine receptors in the inhibition of pro-inflammatory adipokines in 3T3-L1 cells.

Methods: RT-PCR evidenced glycine receptors in 3T3-L1 adipocytes. 3T3-L1 cells were transfected with siRNA for the glycine (Glrb) and TNF1a (Tnfrsf1a) receptors and confirmed by confocal microscopy. Transfected cells were treated with glycine (10 mM). The expressions of TNF-α and IL-6 mRNA were measured by qRT-PCR, while concentrations were quantified by ELISA.

Results: Glycine decreased the expression and concentration of TNF-α and IL-6; this effect did not occur in the absence of TNF-α receptor due to siRNA. In contrast, glycine produced only slight changes in the expression of TNF-α and IL-6 in the absence of the glycine receptor due to siRNA. A docking analysis confirmed the possibility of binding glycine to the TNF-α1a receptor.

Conclusion: These findings support the idea that glycine could partially inhibit the binding of TNF-α to its receptor and provide clues about the mechanisms by which glycine inhibits the secretion of pro-inflammatory adipokines in adipocytes through the TNF-α receptor.

Keywords: Adipokines; Glycine receptor; Inflammation; TNF-α receptor; siRNA.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism*
  • Adiponectin / genetics
  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Gene Expression
  • Glycine / pharmacology*
  • Mice
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • Receptors, Glycine / genetics
  • Receptors, Tumor Necrosis Factor, Type I / antagonists & inhibitors*
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Receptors, Tumor Necrosis Factor, Type II / antagonists & inhibitors*
  • Receptors, Tumor Necrosis Factor, Type II / genetics

Substances

  • Adiponectin
  • Adipoq protein, mouse
  • Cytokines
  • NF-kappa B
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptors, Glycine
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Tnfrsf1a protein, mouse
  • Tnfrsf1b protein, mouse
  • Glycine