Protective effects of genistein on proinflammatory pathways in human brain microvascular endothelial cells

J Nutr Biochem. 2008 Dec;19(12):819-25. doi: 10.1016/j.jnutbio.2007.10.006. Epub 2008 May 13.

Abstract

Proinflammatory cerebromicrovascular environment has been implicated in the critical early pathologic events in a variety of neurodegenerative diseases. Recent studies also have demonstrated the potential beneficial effects of soy isoflavones. However, cellular and molecular mechanisms underlying these processes are not fully understood. The present study was designed to examine the hypothesis that soy isoflavone genistein may attenuate cytokine-induced proinflammatory pathways in human brain microvascular endothelial cells. The quantitative real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay showed that pretreatment of HBMEC with increasing concentrations of genistein significantly and dose-dependently inhibited cytokine-induced up-regulation of mRNA and protein expression of proinflammatory mediators such as tumor necrosis factor-alpha, interleukin-1beta, monocyte chemoattractant protein-1, interleukin-8, and intercellular adhesion molecule-1. In addition, genistein pretreatment significantly reduced cytokine-mediated up-regulation of transmigration of blood leukocytes in a dose-dependent manner. Our results suggest that genistein may attenuate proinflammatory pathways through inhibition of cytokine-induced overexpression of proinflammatory mediators and inflammatory reactions in human brain microvascular endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood-Brain Barrier / drug effects
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Circulation / physiology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology*
  • Enzyme-Linked Immunosorbent Assay
  • Genistein / pharmacology*
  • Humans
  • Inflammation / prevention & control*
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / genetics
  • Leukocytes / drug effects
  • Leukocytes / physiology
  • Microcirculation / drug effects
  • Microcirculation / physiology*
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Interleukin-1beta
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Genistein