Toll IL-1 receptors differ in their ability to promote the stabilization of adenosine and uridine-rich elements containing mRNA
Toll IL-1 receptors differ in their ability to promote the stabilization of adenosine and uridine-rich elements containing mRNA
复制标题
DOI：
10.4049/jimmunol.173.4.2755
复制
发表时间：
2004-08-15
影响因子：
4.4
通讯作者：
Hamilton, TA
中科院分区：
文献类型：
--
作者：
Datta, S;Novotny, M;Hamilton, TA
已知Toll IL-1R （TIR）家族的几种配体可促进含有富au元素（AREs）的短寿命mrna亚群在其3'非翻译区域的稳定。然而，现在很明显，TIR家族的成员可能使用不同的细胞内信号通路来实现生物终点的光谱。通过转染表达不同TIRs的人胚胎肾293细胞，我们现在报道了通过IL-1R1或TLR4而不是TLR3启动的信号可以促进不稳定趋化因子mrna的稳定。当使用小鼠内皮细胞系（H5V）检测内源性受体的信号时，获得了类似的结果。TIR家族成员稳定含are mrna的能力源于它们对信号适配器MyD88、MyD88适配器样蛋白、Toll受体ifn诱导因子（Trif）和Trif相关适配器分子的不同使用。MyD88或MyD88接头样蛋白的过表达能够促进含有are的mRNA的稳定性增强，而Trif和Trif相关接头分子的容量明显降低。因此，tir对mRNA信号稳定的能力似乎与myd88依赖性信号通路有关。
Several ligands for Toll IL-1R (TIR) family are known to promote stabilization of a subset of short-lived mRNAs containing AU-rich elements (AREs) in their 3' untranslated regions. It is now evident however, that members of the TIR family may use distinct intracellular signaling pathways to achieve a spectrum of biological end points. Using human embryonic kidney 293 cells transfected to express different TIRs we now report that signals initiated through IL-1R1 or TLR4 but not TLR3 can promote the stabilization of unstable chemokine mRNAs. Similar results were obtained when signaling from endogenous receptors was examined using a mouse endothelial cell line (H5V). The ability of TIR family members to stabilize ARE-containing mRNAs results from their differential use of signaling adaptors MyD88, MyD88 adaptor-like protein, Toll receptor IFN-inducing factor (Trif), and Trif-related adaptor molecule. Overexpression of MyD88 or MyD88 adaptor-like protein was able to promote enhanced stability of ARE-containing mRNA, whereas Trif and Trif-related adaptor molecule exhibited markedly reduced capacity. Hence the ability of TIRs to signal stabilization of mRNA appears to be linked to the MyD88-dependent signaling pathway.