Wuttge Dirk M, Zhou Xinghua, Sheikine Yuri, Wågsäter Dick, Stemme Veronika, Hedin Ulf, Stemme Sten, Hansson Göran K, Sirsjö Allan
Center for Molecular Medicine and the Department of Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Arterioscler Thromb Vasc Biol. 2004 Apr;24(4):750-5. doi: 10.1161/01.ATV.0000124102.11472.36. Epub 2004 Feb 26.
Atherosclerosis is an inflammatory disease. Several chemokines are important for monocyte/macrophage and T-cell recruitment to the lesion. CXCL16 is a recently discovered chemokine that is expressed in soluble and transmembrane forms, ligates CXCR6 chemokine receptor, and guides migration of activated Th1 and Tc1 cells. It is identical to scavenger receptor SR-PSOX, which mediates uptake of oxidized low-density lipoprotein. We investigated whether CXCL16 expression is controlled by interferon-gamma (IFN-gamma)-cytokine abundant in atherosclerotic lesions.
CXCL16 and CXCR6 expression was identified by polymerase chain reaction and histochemistry in atherosclerotic lesions from humans and apolipoprotein-E-deficient mice. In vitro IFN-gamma induced CXCL16 in human monocytic THP-1 cells and primary human monocytes, which led to increased uptake of oxidized low-density lipoprotein in THP-1 cells, which could be blocked by peptide antibodies against CXCL16. In vivo IFN-gamma induced CXCL16 expression in murine atherosclerotic lesions.
We demonstrate a novel role of IFN-gamma in foam cell formation through upregulation of CXCL16/SR-PSOX. CXCR6 expression in the plaque confirms the presence of cells able to respond to CXCL16. Therefore, this chemokine/scavenger receptor could serve as a molecular link between lipid metabolism and immune activity in the atherosclerotic lesion.
动脉粥样硬化是一种炎症性疾病。几种趋化因子对于单核细胞/巨噬细胞和T细胞募集到病变部位很重要。CXCL16是最近发现的一种趋化因子，以可溶性和跨膜形式表达，连接CXCR6趋化因子受体，并引导活化的Th1和Tc1细胞迁移。它与清道夫受体SR-PSOX相同，后者介导氧化型低密度脂蛋白的摄取。我们研究了CXCL16的表达是否受动脉粥样硬化病变中丰富的干扰素-γ（IFN-γ）细胞因子的控制。
通过聚合酶链反应和组织化学鉴定人及载脂蛋白E缺陷小鼠动脉粥样硬化病变中CXCL16和CXCR6的表达。体外IFN-γ可诱导人单核细胞THP-1细胞和原代人单核细胞中的CXCL16表达，这导致THP-1细胞中氧化型低密度脂蛋白的摄取增加，而针对CXCL16的肽抗体可阻断这种摄取。体内IFN-γ可诱导小鼠动脉粥样硬化病变中CXCL16的表达。
我们证明了IFN-γ通过上调CXCL16/SR-PSOX在泡沫细胞形成中具有新作用。斑块中CXCR6的表达证实了能够对CXCL16作出反应的细胞的存在。因此，这种趋化因子/清道夫受体可作为动脉粥样硬化病变中脂质代谢与免疫活性之间的分子联系。
