Alteration of a macrophages inflammatory protein-related protein-2 (MRP-2) response by high fat and cholesterol diet in mice.
Macrophage inflammatory protein-related protein-2 (MRP-2) is a new member of the CC chemokine family that is recently identified in murine macrophages. MRP-2 is involved in leukocyte trafficking and activation, which can be implicated in inflammatory diseases including atherosclerosis. Little is known about the involvement of this novel chemokine MRP-2 in the pathogenesis of atherosclerosis. To explore the possible association of the MRP-2 with atherosclerosis, we investigated the effects of atherogenic diet on MRP-2 expression in mice. Male C57BL/6 mice were fed a high fat and cholesterol diet (20% fat and 1.5% cholesterol) or a control diet based on AIN-76 for 5, 10, or 14 weeks. The levels of total cholesterol, LDL cholesterol, and F2-isoprostanes in plasma were measured using appropriate enzymatic assays. Tumor necrosis factor alpha (TNF alpha) and MCP-1 release by peritoneal macrophages was determined by ELISA. The mRNA expression level of the MRP-2 was measured by RT-PCR. The levels of total cholesterol, LDL-cholesterol, and 8-iso-prostaglandin F2 alpha in plasma, well-known indexes of atherosclerosis, were significantly increased in the high fat and cholesterol diet group compared to those in the control. A significant increase in the TNF alpha and MCP-1 production by macrophages was also observed in the group fed high fat and cholesterol diet. The mRNA expression of MRP-2 was upregulated by oxLDL treatment in vitro and feeding a high fat and cholesterol diet in vivo at the late stage of atherosclerosis. These results suggest that MRP-2 may be an important contributing factor in the development of atherosclerosis.
Yu
Rina
R
Department of Food Science and Nutrition, University of Ulsan, Mugeo-dong Nam-ku, Ulsan 680-749, South Korea. rinayu@mail.ulsan.ac.kr
Park
Jeong-Soon
JS
Kawada
Teruo
T
Kwon
Byoung-Se
BS
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000517:prevention & control; D018932:Chemokine CCL2 / Q000096:biosynthesis; D019742:Chemokines, CC; D008078:Cholesterol, LDL / Q000097:blood; D016207:Cytokines / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D028421:Isoprostanes / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects
C095218:Ccl9 protein, mouse; D018932:Chemokine CCL2; D019742:Chemokines, CC; D008078:Cholesterol, LDL; D016207:Cytokines; D004041:Dietary Fats; D028421:Isoprostanes; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha