Chemokine Lkn-1/CCL15 enhances matrix metalloproteinase-9 release from human macrophages and macrophage-derived foam cells.
Chemokine Lkn-1/CCL15 enhances matrix metalloproteinase-9 release from human macrophages and macrophage-derived foam cells.
复制标题
DOI：
10.4162/nrp.2008.2.2.134
复制
发表时间：
2008
影响因子：
2.4
通讯作者：
Yu R
中科院分区：
文献类型：
--
作者：
Kwon SH;Ju SA;Kang JH;Kim CS;Yoo HM;Yu R
动脉粥样硬化是一种慢性炎症性疾病，趋化因子在动脉粥样硬化的发生和发展中都起着重要作用。Leukotactin-1 （Lkn-1/CCL15）是人类CC趋化因子家族的新成员，是一种有效的白细胞趋化剂。我们之前的研究表明，Lkn-1/CCL15在动脉粥样硬化的发生中起作用，然而，目前对Lkn-1/CCL15是否与动脉粥样硬化的进展有关知之甚少。人类冠状动脉粥样硬化病变中的基质金属蛋白酶（MMPs）通过改变斑块破裂的易感性在动脉粥样硬化的进展中起着至关重要的作用。在本研究中，我们检测了Lkn-1/CCL15是否调节MMP-9的释放，MMP-9是活化的巨噬细胞和泡沫细胞表达的一种普遍形式。将人THP-1单核细胞和/或人外周血单核细胞（PBMC）用肉豆蔻酸佛波酯处理后诱导其向巨噬细胞分化。用人氧化LDL处理THP-1巨噬细胞制备泡沫细胞。用Lkn-1/CCL15处理巨噬细胞和泡沫细胞，用明胶酶谱法测定MMP-9的释放水平。lkn1 /CCL15显著提高THP-1单核细胞源性巨噬细胞、人pbmc源性巨噬细胞和巨噬细胞源性泡沫细胞的MMP-9蛋白分泌水平，且呈剂量依赖性。我们的数据表明，Lkn-1/CCL15对巨噬细胞和泡沫细胞释放MMP-9的作用可能有助于动脉粥样硬化进展中的斑块不稳定。
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.