Involvement of leukotactin-1, a novel CC chemokine, in human atherosclerosis.
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.
Yu
Rina
R
Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, South Korea. rinayu@ulsan.ac.kr
Kim
Chu-Sook
CS
Kawada
Teruo
T
Kwon
Tae-Won
TW
Lim
Tae-Hwan
TH
Kim
Young-Wook
YW
Kwon
Byung-Se
BS
D000328:Adult; D001161:Arteriosclerosis / Q000473:pathology* / Q000503:physiopathology*; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis; D002340:Carotid Artery Diseases / Q000473:pathology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D019742:Chemokines, CC / Q000032:analysis / Q000378:metabolism*; D002633:Chemotaxis; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment
D015415:Biomarkers; D018932:Chemokine CCL2; D019742:Chemokines, CC; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1