Deng Guo-Min, Zheng Lixin, Chan Francis Ka-Ming, Lenardo Michael
Laboratory of Immunology, Building 10, Room 11N311, 10 Center Drive, MSC 1892, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Med. 2005 Oct;11(10):1066-72. doi: 10.1038/nm1304. Epub 2005 Sep 18.
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.
肿瘤坏死因子（TNF）-α在类风湿性关节炎和脓毒性关节炎等自身免疫性疾病及炎症性疾病的发病机制中起重要作用。TNF-α的生物学效应是通过与TNF受体TNFR1（也称为P60）或TNFR2（也称为P80）结合来介导的。配体前体组装结构域（PLAD）是TNFRs细胞外区域的一部分，介导信号传导所必需的受体链缔合。我们发现，PLAD的可溶性形式，尤其是那些源自P60的形式，在体外可阻断TNF-α的生化效应，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其他涉及TNFR超家族受体的疾病方面具有临床价值。
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