Gamma-aminobutyric acid decreases macrophages infiltration and suppresses inflammatory responses in renal injury

Abstract

The immunomodulatory effects of gamma-aminobutyric acid (GABA) on renal disease were investigated using conditional von Hippel-Lindau gene-knockout C57BL/6 mice (Vhlhdel/del mice), which spontaneously develop fibrosis, inflammation, and hyperplastic clear-cell lesions in the kidneys. Diets containing either GABA rice or pure GABA significantly extended the life span of Vhlhdel/del mice, with decreasing levels of urinary kidney injury molecule (KIM)-1 and renal clear cell formation, which are the typical markers of renal damage. Levels of serum inflammatory markers such as interleukin (IL)-6, renal monocyte chemoattractant protein (MCP)-1, transforming growth factor (TGF)-β, IL-17A, C-C chemokine receptor type 2 (CCR2), and macrophage infiltration were significantly decreased in GABA-fed mice. Further, induction of monocyte migration was significantly suppressed in GABA-treated VHL-silenced HK-2 cells, suggesting that GABA has protective effects against renal injury by disrupting the MCP-1/CCR2 axis and thus macrophage infiltration.

Keywords

• Gamma-aminobutyric acid
• Von Hippel-Lindau
• Monocyte chemotactic protein-1/C-C motif chemokine receptor 2 axis
• Macrophage infiltration