Notch signaling mediates TNF-α-induced IL-6 production in cultured fibroblast-like synoviocytes from rheumatoid arthritis.
Notch signaling mediates TNF-α-induced IL-6 production in cultured fibroblast-like synoviocytes from rheumatoid arthritis.
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DOI：
10.1155/2012/350209
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发表时间：
2012
影响因子：
--
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Jiao Z;Wang W;Ma J;Wang S;Su Z;Xu H
据报道，Notch家族蛋白在类风湿性关节炎（RA）的滑膜组织中表达，并参与滑膜细胞的增殖。本文的目的是研究Notch信号是否介导TNF-α-诱导RA培养成纤维细胞样滑膜细胞（FLSs）产生细胞因子。RA FLSs暴露于TNF-α (10 ng/ml)导致Notch信号靶基因Hes-1升高，Notch 2、Delta-like 1和Delta-like 3 mRNA水平显著上调。γ-分泌酶抑制剂（DAPT）阻断Notch信号通路可抑制RA FLSs对TNF-α的IL-6分泌，而Notch配体δ -like 1的重组融合蛋白处理可促进这种反应。TNF-α刺激也能诱导OA FLSs分泌IL-6；然而，Hes-1水平没有受到影响。我们的数据证实了Notch通路在RA FLSs病理生理中的功能参与，这可能为RA治疗提供新的靶点。
It has been reported that Notch family proteins are expressed in synovium tissue and involved in the proliferation of synoviocyte from rheumatoid arthritis (RA). The aim of this paper was to investigate whether Notch signaling mediated TNF-α-induced cytokine production of cultured fibroblast-like synoviocytes (FLSs) from RA. Exposure of RA FLSs to TNF-α (10 ng/ml) led to increase of Hes-1, a target gene of Notch signaling, and a marked upregulation of Notch 2, Delta-like 1, and Delta-like 3 mRNA levels. Blockage of Notch signaling by a γ-secretase inhibitor (DAPT) inhibited IL-6 secretion of RA FLSs in response to TNF-α while treatment with recombinant fusion protein of Notch ligand Delta-like 1 promoted such response. TNF-α stimulation also induced IL-6 secretion in OA FLSs; however, the Hes-1 level remained unaffected. Our data confirm the functional involvement of Notch pathway in the pathophysiology of RA FLSs which may provide a new target for RA therapy.
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类风湿关节炎患者外周血T辅助细胞中Notch相关分子的表达分析
影响因子：
2.1
作者：
Jiao, Z.;Wang, W.;Li, J.
通讯作者：
Li, J.
DOI：
10.4049/jimmunol.1003658
发表时间：
2011-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Keerthivasan S;Suleiman R;Lawlor R;Roderick J;Bates T;Minter L;Anguita J;Juncadella I;Nickoloff BJ;Le Poole IC;Miele L;Osborne BA
通讯作者：
Osborne BA
影响因子：
1.7
作者：
Yabe, Y;Matsumoto, T;Shindo, H
通讯作者：
Shindo, H
影响因子：
8
作者：
Ando, K;Kanazawa, S;Okamoto, T
通讯作者：
Okamoto, T
影响因子：
2.3
作者：
Fox, David A.;Gizinski, Alison;Morgan, Rachel;Lundy, Steven K.
通讯作者：
Lundy, Steven K.