Nutr Res Pract.  2008 Jun;2(2):134-137.

Chemokine Lkn-1/CCL15 enhances matrix metalloproteinase-9 release from human macrophages and macrophage-derived foam cells

• Kwon SH
• Ju SA
• Kang JH
• Kim CS
• Yoo HM
• Yu R

Abstract

Atherosclerosis is characterized by a chronic inflammatory disease, and chemokines play an important role in both initiation and progression of atherosclerosis development. Leukotactin-1 (Lkn-1/CCL15), a new member of the human CC chemokine family, is a potent chemoattractant for leukocytes. Our previous study has demonstrated that Lkn-1/CCL15 plays a role in the initiation of atherosclerosis, however, little is currently known whether Lkn-1/CCL15 is associated with the progression of atherosclerosis. Matrix metalloproteinases (MMPs) in human coronary atherosclerotic lesions play a crucial role in the progression of atherosclerosis by altering the vulnerability of plaque rupture. In the present study, we examined whether Lkn-1/CCL15 modulates MMP-9 release, which is a prevalent form expressed by activated macrophages and foam cells. Human THP-1 monocytic cells and/or human peripheral blood monocytes (PBMC) were treated with phorbol myristate acetate to induce their differentiation into macrophages. Foam cells were prepared by the treatment of THP-1 macrophages with human oxidized LDL. The macrophages and foam cells were treated with Lkn-1/CCL15, and the levels of MMP-9 release were measured by Gelatin Zymography. Lkn-1/CCL15 significantly enhanced the levels of MMP-9 protein secretion from THP-1 monocytic cells-derived macrophages, human PBMC-derived macrophages, as well as macrophage-derived foam cell in a dose dependent manner. Our data suggest that the action of Lkn-1/CCL15 on macrophages and foam cells to release MMP-9 may contribute to plaque destabilization in the progression of atherosclerosis.

Keyword

Chemokine; Lkn-1/CCL15; MMP-9; foam cell; atherosclerosis

MeSH Terms

Atherosclerosis
Chemokines
Foam Cells
Gelatin
Humans
Leukocytes
Lipoproteins, LDL
Macrophages
Matrix Metalloproteinase 9
Matrix Metalloproteinases
Monocytes
Phorbols
Rupture
Tetradecanoylphorbol Acetate
Chemokines
Gelatin
Lipoproteins, LDL
Matrix Metalloproteinase 9
Matrix Metalloproteinases
Phorbols
Tetradecanoylphorbol Acetate

Figure

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  Fig. 1 Effect of Lkn-1 on the production of MMP-9 protein from human THP-1 monocytic cells-derived macrophages, PBMC-derived macrophags, macrophages-derived foam cells. (A) Human THP-1 monocytic cells were plated at a density of 5 × 105 cells/ml in the medium containing PMA at 10-7M for 48 h to induce their differentiation into macrophages, and then the cells were treated with Lkn-1/CCL15 (100-300 ng/ml) for 24 h or 48 h. (B) Human peripheral blood monocytes were plated at a density of 5 × 105 cells/ml in the medium containing PMA at 10-7M for 48 h to induce their differentiation into macrophages, and then treated with Lkn-1/CCL15 (100-300 ng/ml) for 24 h or 48 h. The gelatinolytic activities of MMP-9 released into the conditioning culture medium were assayed by Gelatin Zymography described in the Materials and Methods. *P < 0.05, significantly different from the control without Lkn-1/CCL15 treatment.

• 

  Fig. 2 Effect of Lkn-1 on the production of MMP-9 protein from macrophages-derived foam cells. Human THP-1 cells were plated at a density of 5 × 105 cells/ml in the medium containing PMA at 10-7M for 48 h to induce their differentiation into macrophages. THP-1 cells-derived macrophages were continuously treated with human oxidized LDL (25 µg/ml) for 4 days to prepare foam cells, and then the foam cells are treated with or without Lkn-1/CCL15 for 16 h. The gelatinolytic activities of MMP-9 released into the conditioning culture medium were assayed by Gelatin Zymography described in the Materials and Methods. *P < 0.05, significantly different from the control without Lkn-1/CCL15 treatment.

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