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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 E 2
Author(s) -
Zhang Yahong,
Wahl Larry M.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0505241
Subject(s) - monocyte , matrix metalloproteinase , prostaglandin e2 , inflammation , ccl2 , tumor necrosis factor alpha , cytokine , endocrinology , chemotaxis , biology , prostaglandin e , prostaglandin , macrophage , medicine , immunology , chemistry , chemokine , receptor , biochemistry , in vitro
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 wasattributable to a differential increase in MCP‐1 and prostaglandin E 2 (PGE 2 ). CRP, at physiological concentrations, induced high levels of MCP‐1 and relatively low levels of PGE 2 , whereas ox‐LDL caused a significant enhancement of PGE 2 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 PGE 2 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 PGE 2 production, which also leads to higher levels of MMP‐1.