Synergistic Effect of Avemar on Proinflammatory Cytokine Production and Ras-mediated Cell Activation

Ann N Y Acad Sci. 2005 Jun;1051:515-28. doi: 10.1196/annals.1361.096.

Abstract

Macrophages activated by lipopolysaccharide and/or phorbol esters exhibited high sensitivity to Avemar, a fermented wheat germ extract. Avemar synergized with lipopolysaccharide and PMA in the induction of the transcription of cytokine genes and release of inflammatory cytokines. At higher concentrations the preparation had a significant negative effect on the proliferation and survival of activated myeloid cell types. Avemar treatment induced the synthesis of ICAM-1 and synergized with the ICAM-inducing effect of TNF, but had no effect on VCAM-1 expression on microvascular endothelial cells. The effect of Avemar on signaling pathways, which are involved in cell activation was studied on HeLa cells as a model system. Avemar treatment increased the activity of stress kinases in a concentration-dependent way, resulting in the activation of AP-1 transcription factor. NF-kappa B-sensitive reporters were also activated by Avemar; in contrast, no effect of the preparation was observed on PKA-sensitive signaling pathways.

MeSH terms

  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Drug Synergism
  • Gene Expression Regulation / drug effects
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Lipopolysaccharides / pharmacology
  • NF-kappa B / metabolism
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins p21(ras) / physiology*
  • Signal Transduction / drug effects
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factor AP-1 / metabolism
  • Vascular Cell Adhesion Molecule-1 / biosynthesis

Substances

  • Avemar
  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • Transcription Factor AP-1
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Proto-Oncogene Proteins p21(ras)
  • Tetradecanoylphorbol Acetate