Amelioration of inflammatory arthritis by targeting the pre-ligand assembly domain of tumor necrosis factor receptors
Amelioration of inflammatory arthritis by targeting the pre-ligand assembly domain of tumor necrosis factor receptors
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DOI：
10.1038/nm1304
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发表时间：
2005-10-01
期刊：
影响因子：
82.9
通讯作者：
Lenardo, M
中科院分区：
文献类型：
--
作者：
Deng, GM;Zheng, LX;Lenardo, M
肿瘤坏死因子（TNF）-α在自身免疫性和炎性疾病如类风湿性和脓毒性关节炎的发病机制中具有重要作用。TNF-α的生物学效应通过与TNF受体TNFR 1（也称为P60）或TNFR 2（也称为P80）结合来介导。前配体组装结构域（PLAD）是TNFR的胞外区的一部分，其介导信号传导所必需的受体-链缔合。我们发现可溶性PLAD，尤其是源自P60的PLAD，可以在体外阻断TNF-α的生化作用，并在动物模型中有效抑制关节炎。因此，靶向PLAD可能在治疗人类关节炎和涉及TNFR超家族受体的其他疾病中具有临床价值。
Tumor necrosis factor (TNF)-alpha has an important role in the pathogenesis of autoimmune and inflammatory diseases such as rheumatoid and septic arthritis. The biological effects of TNF-alpha are mediated by binding to TNF receptors TNFR1 ( also known as P60) or TNFR2 ( also known as P80). The pre-ligand assembly domain (PLAD) is a portion of the extracellular region of TNFRs that mediates receptor-chain association essential for signaling. We found that soluble versions of PLAD, especially those derived from P60, block the biochemical effects of TNF-alpha in vitro and potently inhibit arthritis in animal models. Thus, targeting the PLAD may have clinical value in the treatment of human arthritis and other disorders involving receptors of the TNFR superfamily.