Induction of RANTES by TWEAK/Fn14 interaction in human keratinocytes
Induction of RANTES by TWEAK/Fn14 interaction in human keratinocytes
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DOI：
10.1111/j.0022-202x.2004.22419.x
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发表时间：
2004-05-01
影响因子：
6.5
通讯作者：
Ogawa, H
中科院分区：
文献类型：
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作者：
Jin, L;Nakao, A;Ogawa, H
肿瘤坏死因子样弱凋亡诱导因子（TWEAK）是肿瘤坏死因子（TNF）家族的成员，是一种多功能细胞因子，可调节细胞增殖、血管生成、炎症和凋亡。在这项研究中，我们研究了TWEAK对人角质形成细胞的影响。原代培养的正常人角质形成细胞组成性表达TWEAK受体，成纤维细胞生长因子诱导型14（Fn 14），并产生调节激活，正常T表达和分泌（RANTES）TWEAK刺激后，以浓度依赖性的方式。TWEAK诱导的RANTES产生被抗Fn 14抗体消除，并通过同时刺激转化生长因子β协同增强。此外，在体外分化的人角质形成细胞与高钙含量的培养基显示增强生产RANTES后TWEAK刺激。此外，TWEAK诱导人角质形成细胞中IkappaB-α的快速磷酸化。总的来说，TWEAK通过Fn 14作为RANTES的诱导剂作用于人角质形成细胞。由于RANTES与炎症有关，因此人角质形成细胞中的TWEAK/Fn 14相互作用可能参与炎性皮肤病的病理生理学。
TNF-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) family, is a multifunctional cytokine that regulate cellular proliferation, angiogenesis, inflammation, and apoptosis. In this study, we investigated the effect of TWEAK on human keratinocytes. Primary cultured normal human keratinocytes constitutively expressed a TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14), and produced regulated on activation, normal T expressed and secreted (RANTES) upon TWEAK stimulation in a concentration-dependent manner. The TWEAK-induced RANTES production was abrogated by anti-Fn14 antibody, and synergistically augmented by simultaneous stimulation with transforming growth factor-beta. In addition, human keratinocytes differentiated in vitro with high Ca2+-containing medium showed enhanced production of RANTES upon TWEAK stimulation. Furthermore, TWEAK induced rapid phosphorylation of IkappaB-alpha in human keratinocytes. Collectively, TWEAK acts on human keratinocytes as an inducer of RANTES via Fn14. Because RANTES has been implicated in inflammation, TWEAK/Fn14 interaction in human keratinocytes may be involved in the pathophysiology of inflammatory skin disorders.