Tumor necrosis factor receptor superfamily 14 is involved in atherogenesis by inducing proinflammatory cytokines and matrix metalloproteinases
Tumor necrosis factor receptor superfamily 14 is involved in atherogenesis by inducing proinflammatory cytokines and matrix metalloproteinases
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DOI：
10.1161/hq1201.098945
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发表时间：
2001-12-01
影响因子：
8.7
通讯作者：
Park, JE
中科院分区：
文献类型：
--
作者：
Lee, WH;Kim, SH;Park, JE
肿瘤坏死因子（TNF）受体超家族14（TNFRSF14）是TNF超家族14（LIGHT）的细胞受体。对人颈动脉粥样硬化斑块进行免疫组织化学染色显示，在富含巨噬细胞/泡沫细胞的区域，TNFRSF14高水平表达。为了研究TNFRSF14在单核细胞与动脉粥样硬化形成相关功能中的作用，我们分析了外周血单核细胞或人巨噬细胞样细胞系THP - 1中TNFRSF14受刺激后的表达水平及细胞事件。在活化的单核细胞、由单核细胞衍生的巨噬细胞以及THP - 1细胞中检测到TNFRSF14的高水平表达。用干扰素 - γ和固定化的抗TNFRSF14单克隆抗体同时激活THP - 1细胞，导致促动脉粥样硬化细胞因子（如TNF - α和白细胞介素 - 8）的协同诱导。用固定化的抗TNFRSF14单克隆抗体激活THP - 1细胞可诱导基质金属蛋白酶（MMP）- 1、MMP - 9、MMP - 13以及金属蛋白酶组织抑制剂 - 1和 - 2的表达。此外，对泡沫细胞严重浸润的动脉粥样硬化斑块进行免疫组织化学染色显示，TNFRSF14与MMP - 1、 - 9和 - 13的表达模式重叠。用可溶性LIGHT处理THP - 1细胞也会诱导MMP - 9和白细胞介素 - 8的产生。这些数据表明，TNFRSF14通过诱导促动脉粥样硬化细胞因子以及诱导细胞外基质降解酶降低斑块稳定性而参与动脉粥样硬化。
Tumor necrosis factor (TNF) receptor superfamily 14 (TNFRSF14) is the cellular receptor for TNF superfamily 14 (LIGHT). Immunohistochemical staining of human carotid atherosclerotic plaques revealed a high level of expression of the TNFRSF14 in regions rich in macrophages/foam cells. To investigate the role of TNFRSF14 in the functioning of monocytes in relation to atherogenesis, we have analyzed TNFRSF14 expression levels and cellular events after stimulation of TNFRSF14 in peripheral blood monocytes or the human macrophage-like cell line, THP-1. A high level of expression of TNFRSF14 was detected in activated monocytes, in macrophages derived from monocytes, and in THP-1 cells. Concomitant activation of THP-1 cells with interferon-gamma and immobilized anti-TNFRSF14 monoclonal antibody resulted in synergistic induction of proatherogenic cytokines, such as TNF-alpha and interleukin-8. Activation of THP-I cells with immobilized anti-TNFRSF14 monoclonal antibody induced expression of matrix metalloproteinase (MMP)-1, MMP-9, MMP-13, and tissue inhibitors of metalloproteinase-1 and -2. Furthermore, immunohistochemical staining of atherosclerotic plaques with severe infiltration of foam cells revealed that the expression patterns of TNFRSF14 and MMP-1, -9, and -13 overlapped. Treatment of THP-I cells with soluble LIGHT also caused induction of MMP-9 and interleukin-8. These data suggest that TNFRSF14 is involved in atherosclerosis via the induction of proatherogenic cytokines and decreasing plaque stability by inducing extracellular matrix-degrading enzymes.