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

• Published in: Atherosclerosis 2012-07, Vol.223 (1), p.130-136
• Main Authors: Desai, Anuradha, Darland, Gary, Bland, Jeffrey S, Tripp, Matthew L, Konda, Veera R
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; atherogenesis; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - enzymology; Atherosclerosis - immunology; Atherosclerosis - prevention & control; Biological and medical sciences; biomarkers; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; cell adhesion; Cell Adhesion - drug effects; Cell Communication - drug effects; Cell Line; Coculture Techniques; Coronary heart disease; Dose-Response Relationship, Drug; Down-Regulation; endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - enzymology; Endothelial Cells - immunology; Endothelial function; enzyme activity; fibroblasts; gelatinase B; genes; Heart; Hops; Humans; Humulus - chemistry; immunoassays; inflammation; Inflammation - enzymology; Inflammation - immunology; Inflammation - prevention & control; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - metabolism; interleukin-1beta; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinase Inhibitors; Medical sciences; META060; MMP-9; monocytes; Monocytes - drug effects; Monocytes - enzymology; Monocytes - immunology; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-κB; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; pretreatment; rheumatoid arthritis; screening; TNF-α; Transcription Factor AP-1 - antagonists & inhibitors; Transcription Factor AP-1 - metabolism; transcription factor NF-kappa B; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2012.05.004

Abstract 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.