Anthocyanins from black soybean seed coats preferentially inhibit TNF-alpha-mediated induction of VCAM-1 over ICAM-1 through the regulation of GATAs and IRF-1

J Agric Food Chem. 2009 Aug 26;57(16):7324-30. doi: 10.1021/jf900856z.

Abstract

Adhesion molecules have a key role in pathological inflammation. Thus, we investigated the effect of anthocyanins on the induction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by TNF-alpha and the possible molecular mechanisms by which anthocyanins differentially regulate ICAM-1 and VCAM-1 expression. Stimulation of cells with TNF-alpha increased ICAM-1 and VCAM-1 expression, and pretreatment with anthocyanins inhibited VCAM-1 expression, but not ICAM-1 expression. We found that IRF-1 and GATAs, especially GATA-4 and -6, were involved in the TNF-alpha-mediated expression of VCAM-1 but not ICAM-1, and anthocyanins decreased nuclear levels of GATA-4 and GATA-6 as well as IRF-1. Moreover, pretreatment with a Jak/STAT inhibitor decreased TNF-alpha-induced VCAM-1 expression and nuclear GATA-4, GATA-6, and IRF-1 levels. Furthermore, anthocyanins efficiently inhibited the phosphorylation of STAT-3. This suggests that anthocyanins differentially regulate TNF-alpha-mediated expression of VCAM-1 and ICAM-1 through modulation of the GATA and IRF-1 binding activity via Jak/STAT-3 activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthocyanins / pharmacology*
  • Cells, Cultured
  • Down-Regulation*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • GATA Transcription Factors / genetics
  • GATA Transcription Factors / metabolism*
  • Gene Expression Regulation / drug effects
  • Glycine max / chemistry*
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interferon Regulatory Factor-1 / genetics
  • Interferon Regulatory Factor-1 / metabolism*
  • Plant Extracts / pharmacology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*
  • Vascular Cell Adhesion Molecule-1 / genetics*
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Anthocyanins
  • GATA Transcription Factors
  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1