LIGHT is involved in the pathogenesis of rheumatoid arthritis by inducing the expression of pro-inflammatory cytokines and MMP-9 in macrophages
LIGHT is involved in the pathogenesis of rheumatoid arthritis by inducing the expression of pro-inflammatory cytokines and MMP-9 in macrophages
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DOI：
10.1111/j.1365-2567.2004.02004.x
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发表时间：
2005-02-01
期刊：
影响因子：
6.4
通讯作者：
Lee, WH
中科院分区：
文献类型：
--
作者：
Kim, WJ;Kang, YJ;Lee, WH
在类风湿关节炎（RA）的发展过程中，巨噬细胞在炎症的持续和不可逆的软骨损伤中起着至关重要的作用。已知LIGHT（肿瘤坏死因子超家族成员14，TNFSF14）及其受体TR2（肿瘤坏死因子受体超家族成员14，TNFRSF14）在动脉粥样硬化斑块的泡沫细胞中具有促炎活性。我们验证了一个假设，即LIGHT和TR2参与了类风湿关节炎滑膜中单核细胞/巨噬细胞的活化。对类风湿关节炎滑膜组织样本进行的免疫组织化学分析显示，LIGHT和TR2均在CD68阳性巨噬细胞中表达。相比之下，骨关节炎（OA）患者的滑膜组织样本未显示LIGHT的表达。通过流式细胞术分析也检测到了TR2在类风湿关节炎滑膜巨噬细胞中的表达。为了确定LIGHT在类风湿关节炎巨噬细胞功能中的作用，我们从类风湿关节炎滑液中分离出富含巨噬细胞的细胞，并用LIGHT对其进行刺激。LIGHT诱导了基质金属蛋白酶 - 9以及促炎细胞因子如肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6和IL - 8的表达。这些数据表明，巨噬细胞中表达的LIGHT和TR2通过诱导促炎细胞因子和基质降解酶的表达参与了类风湿关节炎的发病机制。
Macrophages play a crucial role in the perpetuation of inflammation and irreversible cartilage damage during the development of rheumatoid arthritis (RA). LIGHT (TNFSF14) and its receptor TR2 (TNFRSF14) are known to have pro-inflammatory activities in foam cells of atherosclerotic plaques. We tested a hypothesis that LIGHT and TR2 are involved in activation of monocyte/macrophages in RA synovium. Immunohistochemical analysis of RA synovial tissue samples revealed that both LIGHT and TR2 are expressed in CD68 positive macrophages. In contrast, synovial tissue samples from osteoarthritis (OA) patients failed to reveal the expression of LIGHT. Expression of TR2 in RA synovial macrophages was also detected using flow cytometry analysis. To identify the role of LIGHT in the functioning of macrophages in RA, we isolated macrophage enriched cells from RA synovial fluid and stimulated them with LIGHT. LIGHT induced expression of matrix metalloproteinase-9 and pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8. These data indicate that LIGHT and TR2 expressed in macrophages are involved in the pathogenesis of RA by inducing the expression pro-inflammatory cytokines and matrix degrading enzymes.