The apoptotic signaling pathway activated by Toll-like receptor-2
The apoptotic signaling pathway activated by Toll-like receptor-2
复制标题
DOI：
10.1093/emboj/19.13.3325
复制
发表时间：
2000-07-03
期刊：
影响因子：
11.4
通讯作者：
Zychlinsky, A
中科院分区：
文献类型：
--
作者：
Aliprantis, AO;Yang, RB;Zychlinsky, A
先天免疫系统使用Toll家族受体发出微生物存在的信号并启动宿主防御。细菌脂蛋白（BLPs）是toll样受体-2 （TLR2）的有效激活剂，在所有细菌中都有表达。本研究表明，接头分子髓样分化因子88 （MyD88）可通过blp刺激的TLR2介导细胞凋亡和核因子κ B （nf - κ B）活化，抑制MyD88下游的nf - κ B通路可增强细胞凋亡，表明这两条通路在MyD88水平上分叉，TLR2通过与fas相关的死亡结构域蛋白（FADD）和caspase 8相关的通路通过MyD88发出凋亡信号。这些数据表明，TLR2是一种新型的“死亡受体”，它参与了细胞凋亡机制，而没有传统的细胞质死亡结构域。BLP通过TLR2诱导促炎细胞因子白细胞介素-1 β (il -1 β)前体的合成。有趣的是，BLP还通过TLR2激活caspase 1，导致蛋白质水解和成熟IL-1 β的分泌，这些结果表明caspase激活是一种针对微生物病原体的先天免疫反应，最终导致细胞凋亡和细胞因子的产生。
The innate immune system uses Toll family receptors to signal for the presence of microbes and initiate host defense. Bacterial lipoproteins (BLPs), which are expressed by all bacteria, are potent activators of Toll-like receptor-2 (TLR2). Here we show that the adaptor molecule, myeloid differentiation factor 88 (MyD88), mediates both apoptosis and nuclear factor-kappa B (NF-kappa B) activation by BLP-stimuiated TLR2, Inhibition of the NF-kappa B pathway downstream of MyD88 potentiates apoptosis, indicating that these two pathways bifurcate at the level of MyD88, TLR2 signals for apoptosis through MyD88 via a pathway involving Fas-associated death domain protein (FADD) and caspase 8, Moreover, MyD88 binds FADD and is sufficient to induce apoptosis, These data indicate that TLR2, is a novel 'death receptor' that engages the apoptotic machinery without a conventional cytoplasmic death domain. Through TLR2, BLP induces the synthesis of the precursor of the pro-inflammatory cytokine interleukin-1 beta (TL-1 beta). Interestingly, BLP also activates caspase 1 through TLR2, resulting in proteolysis and secretion of mature IL-1 beta, These results indicate that caspase activation is an innate immune response to microbial pathogens, culminating in apoptosis and cytokine production.