META060 attenuates TNF-α-activated inflammation, endothelial-monocyte interactions, and matrix metalloproteinase-9 expression, and inhibits NF-κB and AP-1 in THP-1 monocytes

Atherosclerosis. 2012 Jul;223(1):130-6. doi: 10.1016/j.atherosclerosis.2012.05.004. Epub 2012 May 15.


Background: Cytokine-induced monocyte-endothelial interaction and vascular inflammation play a critical role in atherogenesis. A modified hop extract, META060, was identified as an inhibitor of inflammatory mediators in human rheumatoid arthritis synovial fibroblasts.

Objective: To determine how META060 may impact the initial stages of atherosclerosis, we investigated the effects of META060 in endothelial and monocyte cell models.

Methods: and results: TNF-α (10 ng/mL)-activated human monocytic THP-1 cells adhered to human aortic endothelial cells (HAECs); pre-treatment of cells with META060 (10 μg/mL) significantly inhibited cell adhesion. META060 (1-20 μg/mL) inhibited TNF-α-induced expression of inflammatory mediators including IL-1β, MCP-1 and RANTES in HAECs and THP-1 cells. TNF-α- or LPS-mediated MMP-9 protein levels (measured by an immunoassay) and enzyme activity (determined by zymography) were inhibited by META060 in a dose-dependent manner. Data from transcription factor screening assays showed that META060 selectively inhibited NF-κB and AP-1 in THP-1 cells, suggesting that META060 regulated inflammatory markers through gene regulation.

Conclusion: META060 inhibited monocyte-endothelial cell interactions and suppressed multiple biomarkers of inflammation in both a monocytic cell line and an endothelial cell line. MMP-9 expression and activity also were inhibited. These effects resulted in part from META060's inhibition of transcription factors NF-κB and AP-1. META060 may have beneficial effects for prevention or treatment of cardiovascular diseases by ameliorating inflammation and plaque destabilization, which are hallmarks of atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Atherosclerosis / enzymology
  • Atherosclerosis / immunology
  • Atherosclerosis / prevention & control
  • Cell Adhesion / drug effects
  • Cell Communication / drug effects*
  • Cell Line
  • Coculture Techniques
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Endothelial Cells / drug effects*
  • Endothelial Cells / enzymology
  • Endothelial Cells / immunology
  • Humans
  • Humulus* / chemistry
  • Inflammation / enzymology
  • Inflammation / immunology
  • Inflammation / prevention & control
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors*
  • Monocytes / drug effects*
  • Monocytes / enzymology
  • Monocytes / immunology
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Transcription Factor AP-1 / antagonists & inhibitors*
  • Transcription Factor AP-1 / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*


  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Matrix Metalloproteinase Inhibitors
  • NF-kappa B
  • Plant Extracts
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • Matrix Metalloproteinase 9