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首页> 外文期刊>The FASEB Journal >Tumor necrosis factor receptor 1 associates with CD137 ligand and mediates its reverse signaling
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Tumor necrosis factor receptor 1 associates with CD137 ligand and mediates its reverse signaling

机译：肿瘤坏死因子受体1与CD137配体相关联，并介导其反向信号

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Reverse signaling through CD137 ligand (CD137L) potently activates monocytes. However, the underlying mechanism is not well elucidated. This study provides evidence that tumor necrosis factor receptor 1 (TNFR1) acts as a coreceptor for CD137L and mediates CD137L signaling. CD137L colocalizes with TNFR1 on the plasma membrane and binds directly to TNFR1 via its extracellular domain. Using the human monocytic THP-1 cell line, we demonstrate that engagement of CD137L by recombinant CD137 protein promotes cell adhesion, apoptosis, expression of CD14, and production of IL-8 and tumor necrosis factor (TNF). Concomitantly, the expression of TNFR1 protein is down-regulated in response to CD137L activation, due to enhanced extracellular release and internalization of TNFR1. Activation of TNFR1 by TNF protein additively augments CD137L-induced IL-8 expression. Conversely, inhibition of TNFR1 activity by a TNFR1-neutralizing antibody inhibits CD137L-mediated cell adhesion, cell death, CD14 expression, and IL-8 production. Taken together, these data show that TNFR1 associates with CD137L and is required for CD137L reverse signaling.—Moh, M. C., Lorenzini, P. A., Gullo, C., Schwarz, H. Tumor necrosis factor receptor 1 associates with CD137 ligand and mediates its reverse signaling.
机译：通过CD137配体（CD137L）逆向信号效果地激活单核细胞。然而，潜在的机制并不熟悉。本研究提供了肿瘤坏死因子受体1（TNFR1）作为CD137L的核心感受，并介导CD137L信号传导。 CD137L在血浆膜上用TNFR1分析，通过其细胞外结构域直接与TNFR1直接结合。使用人单核细胞THP-1细胞系，我们证明CD137L通过重组CD137蛋白的接合促进了细胞粘附，凋亡，CD14的表达，以及IL-8和肿瘤坏死因子（TNF）的产生。同时，由于增强的细胞外释放和TNFR1的内化，TNFR1蛋白的表达响应于CD137L活化而下调。 TNF蛋白的TNFR1激活CD137L诱导的IL-8表达。相反，TNFR1中和抗体对TNFR1活性的抑制抑制CD137L介导的细胞粘附，细胞死亡，CD14表达和IL-8产生。总之，这些数据表明，TNFR1与CD137L相关联，并且是CD137L反向信号传导。-MOH，MC，Lorenzini，PA，Gullo，C.，Schwarz，H.肿瘤坏死因子受体1与CD137配体相关联，并介导其逆转信令。

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