Involvement of suppressor of cytokine signaling-1-mediated degradation of MyD88-adaptor-like protein in the suppression of Toll-like receptor 2-mediated signaling by the murine C-type lectin SIGNR1-mediated signaling
Involvement of suppressor of cytokine signaling-1-mediated degradation of MyD88-adaptor-like protein in the suppression of Toll-like receptor 2-mediated signaling by the murine C-type lectin SIGNR1-mediated signaling
复制标题
细胞因子信号传导抑制因子 1 介导的 MyD88 适配器样蛋白降解参与小鼠 C 型凝集素 SIGNR1 介导的信号传导抑制 Toll 样受体 2 介导的信号传导
DOI：
10.1111/j.1462-5822.2011.01695.x
复制
发表时间：
2012
影响因子：
3.4
通讯作者：
K Shibata
中科院分区：
文献类型：
--
作者：
M Ohtani;M Iyori;A Saeki;N Tanizume;T Into;A Hasebe;Y Totsuka;K Shibata
树突状细胞通过Toll样受体等模式识别受体识别病原体，并通过吞噬受体吞噬和消化病原体进行抗原呈递。这项研究旨在阐明树突状细胞中微生物的识别和吞噬之间的相互作用。用鼠C型凝集素SIGNR 1配体脂阿拉伯甘露聚糖和Toll样受体2配体FSL-1刺激鼠树突状细胞系XS 106细胞。共刺激以剂量依赖性方式显著抑制FSL-1介导的NF-κB活化以及TNF-α、IL-6和IL-12 p40的产生。通过敲低SIGNR 1，抑制显著但未完全恢复。在XS 106细胞中，SIGNR 1与Toll样受体2相关。共刺激上调了XS 106细胞中细胞因子信号转导抑制因子-1的表达，其敲低几乎完全恢复了脂阿拉伯甘露聚糖对FSL-1介导的细胞因子产生的抑制。此外，发现在不存在但不存在蛋白酶体抑制剂MG 132的情况下，XS 106细胞中的MyD 88接头样蛋白通过FSL-1和脂阿拉伯甘露聚糖的共刺激而降解，并且降解通过敲低细胞因子信号传导抑制因子-1而被抑制。这项研究表明，Toll样受体2介导的信号传导受到树突状细胞中SIGNR 1介导的信号传导的负调控，可能是通过抑制细胞因子信号传导1介导的MyD 88适配器样蛋白降解。
Dendritic cells recognize pathogens through pattern recognition receptors such as Toll‐like receptors and phagocytose and digest them by phagocytic receptors for antigen presentation. This study was designed to clarify the cross‐talk between recognition and phagocytosis of microbes in dendritic cells. The murine dendritic cell line XS106 cells were stimulated with the murine C‐type lectin SIGNR1 ligand lipoarabinomannan and the Toll‐like receptor 2 ligand FSL‐1. The co‐stimulation significantly suppressed FSL‐1‐mediated activation of NF‐κB as well as production of TNF‐α, IL‐6 and IL‐12p40 in a dose‐dependent manner. The suppression was significantly but not completely recovered by knock‐down of SIGNR1. SIGNR1 was associated with Toll‐like receptor 2 in XS106 cells. The co‐stimulation upregulated the expression of suppressor of cytokine signalling‐1 in XS106 cells, the knock‐down of which almost completely recovered the suppression of the FSL‐1‐mediated cytokine production by lipoarabinomannan. In addition, it was found that the MyD88‐adaptor‐like protein in XS106 cells was degraded by co‐stimulation with FSL‐1 and lipoarabinomannan in the absence, but not the presence, of the proteasome inhibitor MG132 and the degradation was inhibited by knock‐down of suppressor of cytokine signalling‐1. This study suggests that Toll‐like receptor 2‐mediated signalling is negatively regulated by SIGNR1‐mediated signalling in dendritic cells, possibly through suppressor of cytokine signalling‐1‐mediated degradation of the MyD88‐adaptor‐like protein.