Pro-inflammatory effect of TWEAK/Fn14 interaction on human umbilical vein endothelial cells
Pro-inflammatory effect of TWEAK/Fn14 interaction on human umbilical vein endothelial cells
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DOI：
10.1016/s0006-291x(02)02670-0
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发表时间：
2002-12-06
影响因子：
3.1
通讯作者：
Okumura, K
中科院分区：
文献类型：
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作者：
Harada, N;Nakayama, M;Okumura, K
作为肿瘤坏死因子家族的一员，TWAKE可诱导某些肿瘤细胞死亡，但也可诱导血管内皮细胞增殖和血管生成。近年来，成纤维细胞生长因子诱导因子14(Fn14)被发现是一种TWEY受体，可能与内皮细胞的增殖和血管生成有关。在本研究中，我们研究了TWEK对人脐静脉内皮细胞(HUVEC)的促炎作用。我们发现TWEEP不仅可以诱导HUVEC的增殖和迁移，还可以上调细胞表面ICAM-1和E-选择素等黏附分子的表达，并诱导HUVEC分泌IL-8和MCP-1等趋化因子。此外，通过使用抗Fn14单抗阻断TWEE/Fn14相互作用，我们证明了Fn14在HUVEC上有结构性表达，并完全介导了TWEK对HUVEC的生物学效应。这些结果表明，TWEK可通过Fn14诱导HUVEC的促炎反应。(C)2002年埃尔塞维尔科学公司(美国)。版权所有。
TWEAK, a member of the TNF family, induces cell death in some tumor cell lines, but also induces proliferation of endothelial cells and angiogenesis. Recently, fibroblast growth factor-inducible 14 (Fn14) has been identified to be a TWEAK receptor, which may be responsible for the proliferation of endothelial cells and angiogenesis. In this study, we investigated the pro-inflammatory effect of TWEAK on human umbilical vein endothelial cells (HUVEC). We demonstrated that TWEAK could not only induce the proliferation and migration but also upregulate the cell surface expression of adhesion molecules such as ICAM-1 and E-selectin, and induce the secretion of chemokines such as IL-8 and MCP-1 in HUVEC. Moreover, by using an anti-Fn14 mAb that blocks the TWEAK/Fn14 interaction, we demonstrated that Fn14 was constitutively expressed on HUVEC and totally mediated the biological effects of TWEAK on HUVEC. These results indicated that TWEAK could induce pro-inflammatory reactions via Fn14 on HUVEC. (C) 2002 Elsevier Science (USA). All rights reserved.