Matrix metalloproteinase-1 expression by interaction between monocytes and vascular endothelial cells.
There is accumulating evidence of complicated interactions among vascular cells, i.e. endothelial cells, smooth muscle cells and monocytes/macrophages, in the regulation of vascular function and remodeling. We have investigated the mechanisms responsible for matrix metalloproteinase (MMP)-1 expression by interactions between monocytes and vascular endothelial cells. THP-1 cells (human monocytic cell line) and human umbilical vein endothelial cells (HUVECs) were cocultured. MMP-1 levels in the culture medium were measured by enzyme-linked immunosorbent assays. Collagenolytic activity in the culture medium was measured by fluorescence labeled-collagen digestion. Immunohistochemistry using an anti-MMP antibody was carried out to determine which types of cell produce MMP-1. The addition of THP-1 cells to HUVECs for 48 h induced increases in MMP-1 levels and collagenolytic activity, which were 5- and 2-fold relative to those of HUVECs alone, respectively. A separate coculture experiment revealed that direct contact of THP-1 cells and HUVECs contributed to enhanced MMP-1 production in the cocolture. Immunohistochemical analysis revealed that both types of cell produce MMP-1 in the coculture. Neutralizing anti-interleukin-1 beta and tumor necrosis factor- alpha antibodies inhibited MMP-1 production by the coculture. The Src kinase and MEK inhibitors significantly inhibited MMP-1 production by the coculture. Coculture of THP-1 cells and HUVECs induced significant increases in Src and mitogen activated protein (MAP) kinase activities. Enhanced MMP-1 expression induced by monocyte-endothelial cell interactions may play an important role in the pathogenesis of atherosclerosis and plaque rupture.
Hojo
Y
Y
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Ikeda
U
U
Takahashi
M
M
Sakata
Y
Y
Takizawa
T
T
Okada
K
K
Saito
T
T
Shimada
K
K
D001161:Arteriosclerosis / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D009000:Monocytes / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D019061:src-Family Kinases; D020781:Matrix Metalloproteinase 1