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A Modified Hop Extract (Meta060) Inhibits Hyperglycemia Mediated Monocyte‐Endothelial Interactions and LPS Mediated MMP‐9 Secretion in Human THP‐1 Monocytes
Author(s) -
Desai Anuradha,
Konda Veera Reddy,
Bland Jeffrey,
Tripp Matthew
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.700.11
Subject(s) - monocyte , thp1 cell line , inflammation , matrix metalloproteinase , secretion , signal transduction , mapk/erk pathway , chemistry , microbiology and biotechnology , protein kinase c , pharmacology , cell culture , medicine , biology , immunology , biochemistry , genetics
It is now recognized that diabetes increases atherosclerosis complications by increasing the inflammation which activate matrix matalloproteinases (MMPs), causing instability in the plaque. Previously, we reported that various analogs of reduced iso‐alpha acid analogs have potent anti‐inflammatory properties in vitro. In this study, we evaluated the effect of Meta060, a modified hop extract on hyperglycemia mediated activation of monocyte, THP‐1 cells. Subjecting THP‐1 cells to hyperglycemic conditions activated the binding of THP‐1 to human aortic endothelial cells (HAEC). We found that Meta060 reduced the hyperglycemia mediated monocyte interactions to HAEC. We also evaluated the effects of Meta060 on LPS activated matrix metalloproteinase secretion in THP‐1 cells. Meta060 dose dependently reduced the expression and activity of MMP‐9 in THP‐1 cells. To understand the cell signaling pathways, we evaluated the Meta060 in cell free kinase assays. Meta060 dose dependently inhibited kinases involved in inflammatory signaling pathways, PKC, MAPK and NF‐κB. The data demonstrated that Meta060 inhibits inflammation in monocytes, monocyte‐endothelial interactions, and reduces monocyte MMP‐9 production, which could prevent the destabilization of plaque. These results suggest that Meta060 may be a useful treatment to reduce complications related to atherosclerosis (Supported by Metagenics Inc.)