Article

Involvement of leukotactin-1, a novel CC chemokine, in human atherosclerosis

Kyungpook National University, Daikyū, Daegu, South Korea
Atherosclerosis (Impact Factor: 3.99). 06/2004; 174(1):35-42. DOI: 10.1016/j.atherosclerosis.2003.11.024
Source: PubMed

ABSTRACT

Atherosclerosis is a chronic inflammatory disease that involves the recruitment of leukocytes to the arterial wall. Leukotactin-1 (Lkn-1), a new member of the CC chemokine family, is a potent chemoattractant for leukocytes and thus is implicated in inflammatory diseases. In this study, we investigated the possible association of Lkn-1 with human atherosclerosis. Atherosclerotic lesion and plasma samples were obtained from atherosclerotic patients. Human THP-1 monocyte-derived foam cells were prepared by treatment with an oxidized low-density lipoprotein. The expression level of Lkn-1 or its receptors mRNA was measured by RT-PCR analysis. Levels of plasma Lkn-1, MCP-1, ICAM-1 and total cholesterol were measured by ELISA or enzymatic assay. Lkn-1 expression was markedly enhanced not only at the mRNA level in human atherosclerotic lesions, but also at the circulating level in atherosclerosis patients compared with normal subjects. An in vitro study revealed that the level of Lkn-1 release was significantly enhanced by oxidative stress or proatherogenic mediators in macrophages and macrophage-derived foam cells. Lkn-1 stimulated endothelial cells to release ICAM-1, which is implicated in atherogenesis. Taken together, our data suggest that Lkn-1 plays an important role in the development of atherosclerosis.

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    • "The fact that IL-6 is produced by several organs might contribute to its complex effects on metabolic regulation. MCP-1 decreases insulin-stimulated glucose uptake in adipocytes[49], and plays a pivotal role in the development of atherosclerosis via the enhancement of adhesion molecules on leukocytes and endothelial cells[50]. However, recent studies investigating the role of MCP-1 on insulin resistance have produced inconsistent results[51,52]. "
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    • "* P < 0.05, significantly different from the control without Lkn-1/CCL15 treatment. phages and macrophage-derived foam cells (Yu et al., 2004). Therefore, it can be postulated that macrophages and macrophage-derived foam cells in atherosclerotic lesions may enhance the local concentration of Lkn-1 in the lesions, and Lkn-1/CCL15 subsequently stimulate the macrophages/foam cells per se to secrete MMP-9, indicating that Lkn-1/CCL15 action on macrophages and foam cells to release MMP-9 may contribute to plaque destabilization in the progression of atherosclerosis. "
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