TIRAP在激活TLR2和TLR4共享的信号级联中的重要作用
Masahiro Yamamoto1, Shintaro Sato, Hiroaki Hemmi
1Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan Science and Technology Corporation, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Nature
|November 26, 2002
概括
收费类受体 (TLR) 信号适应器 TIRAP (收费类介质-1受体域含适应蛋白) 对于TLR2和TLR4信号中的MyD88依赖途径至关重要,而不是MyD88独立途径.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 托尔类受体 (TLRs) 通过它们的托尔/互白素-1受体 (TIR) 域来调解免疫反应.
- MyD88是TLR信号传递中常见的适应蛋白,但一些LPS响应在缺少它的情况下仍然存在.
- 假设TIRAP (Mal) 可以调解MyD88独立的TLR4信号传输.
研究的目的:
- 研究TIRAP在TLR信号通路中的作用.
- 为了确定TIRAP是否参与MyD88独立反应.
- 澄清特定的TLR和利用TIRAP的信号通路.
主要方法:
- 在TIRAP缺乏的小鼠中分析LPS诱导的反应.
- 评估细胞增殖和细胞因子的产生.
- 对NF-kappaB和MAPK激活动态的评估.
- 检查干扰素诱导基因表达和树突细胞成熟.
- 测试对各种TLR激活剂 (TLR2,TLR3,TLR7,TLR9) 的反应.
主要成果:
- 在TIRAP缺乏的小鼠中,LPS诱导的脊髓细胞增殖和细胞因子生产被废除.
- 在TIRAP缺乏的小鼠中,NF-kappaB和MAPK激活显示出延迟的动力学,类似于MyD88缺乏的小鼠.
- 在TIRAP缺乏的小鼠中,干扰素诱导基因表达和树突细胞成熟正常发生.
- 缺乏TIRAP的小鼠对TLR2连接体有缺陷反应,但对TLR3,TLR7或TLR9激动剂没有.
- TIRAP对于TLR2和TLR4共同的MyD88依赖信号通路至关重要.
结论:
- TIRAP不是针对TLR4信号的特异性.
- TIRAP没有调解MyD88独立的TLR信号.
- TIRAP在TLR2和TLR4激活的MyD88依赖途径中发挥着关键作用.
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