Synergistic enhancement of cytokine-induced human monocyte matrix metalloproteinase-1 by C-reactive protein and oxidized LDL through differential regulation of monocyte chemotactic protein-1 and prostaglandin E2
- 21 October 2005
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 79 (1), 105-113
- https://doi.org/10.1189/jlb.0505241
Abstract
C-reactive protein (CRP) and oxidized LDL (ox-LDL) are associated with inflammatory lesions, such as coronary artery disease, in which monocytes and matrix metalloproteinases (MMPs) may play a major role in the rupture of atherosclerotic plaques. Monocytes are recruited to inflammation sites by monocyte chemoattractant protein-1 (MCP-1), which may also participate in the activation of monocytes. The objective of this study was to compare the individual and combined effect of CRP and ox-LDL on human monocyte MMP-1 and the role of MCP-1 in this effect. Although CRP or ox-LDL failed to induce MMP-1 in control monocytes, these molecules enhanced MMP-1 production induced by tumor necrosis factor α (TNF-α) and granulocyte macrophage-colony stimulating factor (GM-CSF) with a synergistic increase in MMP-1 occurring in the presence of both mediators. Enhancement of MMP-1 by CRP and ox-LDL was attributable to a differential increase in MCP-1 and prostaglandin E2(PGE2). CRP, at physiological concentrations, induced high levels of MCP-1 and relatively low levels of PGE2, whereas ox-LDL caused a significant enhancement of PGE2 with little affect on MCP-1. Accordingly, CRP- and ox-LDL-induced MMP-1 production by monocytes was inhibited by anti-MCP-1 antibodies and indomethacin, respectively. Moreover, addition of exogenous MCP-1 or PGE2 enhanced MMP-1 production by TNF-α- and GM-CSF-stimulated monocytes. These results show that the combination of CRP and ox-LDL can cause a synergistic enhancement of the role of monocytes in inflammation, first, by increasing MCP-1, which attracts more monocytes and directly enhances MMP-1 production by activated monocytes, and second, by elevating PGE2 production, which also leads to higher levels of MMP-1.Keywords
Funding Information
- Intramural Research Program of the NIH
- NIDCR
This publication has 43 references indexed in Scilit:
- High-sensitivity C-reactive protein: Clinical importanceCurrent Problems in Cardiology, 2004
- C-Reactive Protein Promotes Monocyte Chemoattractant Protein-1—Mediated Chemotaxis Through Upregulating CC Chemokine Receptor 2 Expression in Human MonocytesCirculation, 2004
- Protein Kinase C β Is Required for Human Monocyte Chemotaxis to MCP-1Journal of Biological Chemistry, 2003
- Chemokine Receptor CCR2 Expression and Monocyte Chemoattractant Protein-1–Mediated Chemotaxis in Human MonocytesArteriosclerosis, Thrombosis, and Vascular Biology, 1998
- The effects of oxidized low density lipoproteins on inducible mouse macrophage gene expression are gene and stimulus dependent.JCI Insight, 1995
- Human Monocytes Produce Monocyte Chemoattractant Protein 1 (MCP-1) in Response to a Synthetic Peptide Derived from C-Reactive ProteinClinical Immunology and Immunopathology, 1995
- Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques.JCI Insight, 1994
- Oxidized LDL enhances lipopolysaccharide-induced tissue factor expression in human adherent monocytes.Arteriosclerosis and Thrombosis: A Journal of Vascular Biology, 1994
- Synergism Between Platelet Activating Factor and C-C Chemokines for Arachidonate Release in Human MonocytesBiochemical and Biophysical Research Communications, 1994
- Internalization and degradation of receptor bound C-reactive protein by U-937 cells: induction of H2O2 production and tumoricidal activityBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1991