IL-1 receptor accessory protein is an essential component of the IL-1 receptor.
IL-1 receptor accessory protein is an essential component of the IL-1 receptor.
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DOI：
10.4049/jimmunol.161.10.5614
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发表时间：
1998-11
影响因子：
4.4
通讯作者：
Emily B. Cullinan;Lia Kwee;P. Nunes;David J. Shuster;Grace Ju;Kim W. McIntyre;R. Chizzonite;Mark Labow
中科院分区：
文献类型：
--
作者：
Emily B. Cullinan;Lia Kwee;P. Nunes;David J. Shuster;Grace Ju;Kim W. McIntyre;R. Chizzonite;Mark Labow
最近描述的IL-1R辅助蛋白（IL-1R AcP）与IL-1 β和IL-1型ir （IL-1RI）相互作用，但IL-1R AcP在IL-1信号传导中的基本要求尚未确定，其在体内的作用也未被研究。本研究制备了IL-1R acp缺陷小鼠和成纤维细胞，并对其进行了表征。所有IL-1激动剂都通过I型IL-1R与IL-1R acp缺陷细胞结合，但无法通过核因子- kappab或ap -1依赖的信号通路激活基因表达。缺乏IL-1R AcP对IL-1配体的亲和力有不同的影响。与野生型细胞相比，IL-1R acp缺陷成纤维细胞结合小鼠il -1 α和人IL-1R拮抗剂蛋白（IL-1Ra）的亲和力仅中度降低，而小鼠il -1 β的亲和力降低了70倍。IL-1在IL-1R acp缺陷小鼠体内也不能产生生物学反应。这些数据表明，I型IL-1R/IL-1R AcP复合物是所有IL-1激动剂的信号传导和IL-1 β高亲和力结合所必需的。最后，IL-1R AcP是功能性IL-1R的重要信号转导成分，可能是阻断人类疾病中IL-1功能的新靶点。
The recently described IL-1R accessory protein (IL-1R AcP) interacts with IL-1beta and the IL-1 type-IR (IL-1RI), but an essential requirement for IL-1R AcP in IL-1 signaling in vitro has not been established and its role in vivo has not been examined. In this study, IL-1R AcP-deficient mice and fibroblasts were produced and characterized. All IL-1 agonists bound to IL-1R AcP-deficient cells through the type I IL-1R, but failed to activate gene expression through either the nuclear factor-kappaB or AP-1-dependent signaling pathways. Absence of IL-1R AcP differentially affected the affinity for IL-1 ligands. IL-1R AcP-deficient fibroblasts bound murine IL-1alpha and human IL-1R antagonist protein (IL-1Ra) with only moderately reduced affinity when compared with wild-type cells, whereas murine IL-1beta affinity was reduced by 70-fold. IL-1 also failed to produce a biologic response in vivo in IL-1R AcP-deficient mice. These data demonstrate that a type I IL-1R/IL-1R AcP complex is required for signaling by all IL-1 agonists and for high affinity binding by IL-1beta. Finally, IL-1R AcP is an essential signal transducing component of the functional IL-1R and should represent a novel target for blocking IL-1 function in human disease.