Shi Zhongcheng, Cai Zhenyu, Wen Shu, Chen Caoyi, Gendron Christi, Sanchez Amir, Patterson Kevin, Fu Songbin, Yang Jianhua, Wildman Derek, Finnell Richard H, Zhang Dekai
Center for Infectious and Inflammatory Disease, Institute of Bioscience and Technology, Texas A&M University Health Science Center, Houston, Texas 77030, USA.
J Biol Chem. 2009 Jul 31;284(31):20540-7. doi: 10.1074/jbc.M109.022541. Epub 2009 Jun 1.
Little has been known about Tlr13 (Toll-like receptor 13), a novel member of the Toll-like receptor family. To elucidate the molecular basis of murine Tlr13 gene expression, the activity of the Tlr13 gene promoter was characterized. Reporter gene analysis and electrophoretic mobility shift assays demonstrated that Tlr13 gene transcription was regulated through three cis-acting elements that interacted with the Ets2, Sp1, and PU.1 transcription factors. Furthermore, our work suggests that these transcription factors may cooperate, culminating in maximal transcription of the Tlr13 gene. In contrast, NF-kappaB appeared to act as an inhibitor of Tlr13 transcription. Overexpression of Ets2 caused a strong increase in the transcriptional activity of the Tlr13 promoter; however, overexpression of NF-kappaB p65 dramatically inhibited it. Additionally, interferon-beta is capable of acting Tlr13 transcription, but the activated signaling of lipopolysaccharide/TLR4 and peptidoglycan/TLR2 strongly inhibited the Tlr13 gene promoter. Thus, these findings reveal the mechanism of Tlr13 gene regulation, thereby providing insight into the function of Tlr13 in the immune response to pathogen.
关于Toll样受体家族的新成员Tlr13（Toll样受体13），人们了解甚少。为阐明小鼠Tlr13基因表达的分子基础，对Tlr13基因启动子的活性进行了表征。报告基因分析和电泳迁移率变动分析表明，Tlr13基因转录受三个顺式作用元件调控，这些元件与Ets2、Sp1和PU.1转录因子相互作用。此外，我们的研究表明，这些转录因子可能协同作用，最终导致Tlr13基因的最大转录。相比之下，NF-κB似乎是Tlr13转录的抑制剂。Ets2的过表达导致Tlr13启动子的转录活性大幅增加；然而，NF-κB p65的过表达则显著抑制了它。此外，干扰素-β能够作用于Tlr13转录，但脂多糖/TLR4和肽聚糖/TLR2的激活信号强烈抑制了Tlr13基因启动子。因此，这些发现揭示了Tlr13基因调控的机制，从而为深入了解Tlr13在病原体免疫反应中的功能提供了线索。
