Inhibition of TNFα-induced interleukin-6 gene expression by barley (Hordeum vulgare) ethanol extract in BV-2 microglia

Genes Genomics. 2019 May;41(5):557-566. doi: 10.1007/s13258-018-00781-8. Epub 2019 Feb 22.

Abstract

Background: Inflammation in the central nervous system is closely associated with pathological neurodegenerative diseases as well as psychiatric disorders. Prolonged activation of microglia can produce many inflammatory mediators, which may result in pathological neurotoxic side effects. Interleukin (IL)-6 serves as a hallmark of the injured brain.

Objective: Whole grains are known to contain many bioactive components. However, little information is available about anti-neuroinflammatory effects of grains in the CNS. This study aims to investigate the effect of Hordeum vulgare ethanol extract (HVE) on the suppression of IL-6 expression in BV2 microglia.

Methods: Inhibitory effects of HVE on IL-6 expression were analyzed by immunoblot anaysis, immunofluoresce microscopic analysis, reverse transcription-polymerase chain reaction, and luciferase promoter reporter assay.

Results: HVE inhibited TNFα-induced phosphorylation of IKKα/β, IκB, and p65/RelA NF-κB. TNFα-induced IL-6 mRNA expression and promoter activity were reduced by HVE. Point mutation of NF-κB-binding site within the IL-6 gene promoter abolished TNFα-induced reporter activity, whereas exogenous expression of p65 NF-κB enhanced IL-6 promoter activity.

Conclusion: NF-κB-binding site within the IL-6 promoter region is a HVE target element involved in the inhibition of TNFα-induced IL-6 gene transcription. HVE inhibits TNFα-induced IL-6 expression via suppression of NF-κB signaling in BV2 microglial cells.

Keywords: Hordeum vulgare; Interleukin-6; Microglia; NF-κB; Neuroinflammation; TNFα.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Cell Line
  • Edible Grain / metabolism
  • Gene Expression Regulation / drug effects
  • Hordeum / metabolism*
  • Hordeum / physiology
  • I-kappa B Kinase / metabolism
  • I-kappa B Proteins / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Microglia / drug effects*
  • Phosphorylation / drug effects
  • Plant Extracts / pharmacology
  • Promoter Regions, Genetic / genetics
  • Rats
  • Signal Transduction
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • I-kappa B Proteins
  • Interleukin-6
  • Plant Extracts
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • CHUK protein, human
  • I-kappa B Kinase