Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
J Biol Chem. 2013 Feb 22;288(8):5616-23. doi: 10.1074/jbc.M112.403899. Epub 2013 Jan 14.
The proinflammatory danger signal IL-33, which is released from damaged or dying cells, achieves its effects via the IL-1R family member ST2L. The detection of IL-33 by ST2L initiates downstream signaling pathways that result in the activation of MAPKs and NF-κB. Here, we show that TMED1 associates with ST2L. Using a series of mutation and deletion constructs, we demonstrate that this interaction is mediated by the GOLD domain of TMED1 and the TIR domain of ST2L. Our findings also demonstrate that TMED1 is required for optimal IL-33-induced IL-8 and IL-6 production. This discovery provides additional support to the concept that the TMED family members are important players in innate immune signaling.
促炎危险信号 IL-33 由受损或死亡的细胞释放，通过 IL-1R 家族成员 ST2L 发挥作用。ST2L 通过检测 IL-33 启动下游信号通路，导致 MAPKs 和 NF-κB 的激活。在这里，我们发现 TMED1 与 ST2L 相关。通过一系列突变和缺失构建，我们证明这种相互作用是由 TMED1 的 GOLD 结构域和 ST2L 的 TIR 结构域介导的。我们的研究结果还表明，TMED1 是 IL-33 诱导 IL-8 和 IL-6 产生的最佳所必需的。这一发现为 TMED 家族成员是先天免疫信号中的重要参与者的概念提供了额外的支持。
