CpG oligonucleotides induce an immune response of odontoblasts through the TLR9, MyD88 and NF-κB pathways
CpG oligonucleotides induce an immune response of odontoblasts through the TLR9, MyD88 and NF-κB pathways
复制标题
DOI：
10.1016/j.bbrc.2010.07.068
复制
发表时间：
2010-08-20
影响因子：
3.1
通讯作者：
Wang, Ping
中科院分区：
文献类型：
--
作者：
He, Wenxi;Yu, Qing;Wang, Ping
成牙本质细胞是抵抗微生物入侵的第一道防线细胞。Toll样受体（TLR）在先天免疫中起着至关重要的作用，TLR 9参与微生物DNA的识别。本研究旨在探讨成牙本质细胞是否对CpG DNA产生应答，并探讨CpG DNA引发的细胞内信号转导途径。我们发现小鼠成牙本质细胞样细胞系MDPC-23组成型表达TLR 9。暴露于CpG ODN诱导了基于IL-6和TNF-α表达增加的有效促炎反应。用抑制性MyD 88肽或TLR 9、NF-κ B或I κ B α的特异性抑制剂预处理显著抑制CpG ODN诱导的IL-6和TNF-α表达。此外，CpG ODN介导的MDPC-23细胞中kappa B-荧光素酶活性的增加被TLR 9显性失活突变体的过表达抑制。MyD 88和I κ B α，但不受TLR 4的显性失活突变体的影响。这一结果提示CpG DNA介导的免疫应答在成牙本质细胞中可能发挥作用，并表明TLR 9、MyD 88和NF-κ B B参与了这一过程。皇冠版权所有（C）2010由爱思唯尔公司出版。All rights reserved.
Odontoblasts are the first-line defense cells against invading microorganisms. Toll-like receptors (TLRs) play a crucial role in innate immunity, and TLR9 is involved in the recognition of microbial DNA. This study aimed to investigate whether odontoblasts can respond to CpG DNA and to determine the intracellular signaling pathways triggered by CpG DNA. We found that the mouse odontoblast-like cell line MDPC-23 constitutively expressed TLR9. Exposure to CpG ODN induced a potent proinflammatory response based on an increase of IL-6 and TNF-alpha expression. Pretreatment with an inhibitory MyD88 peptide or a specific inhibitor for TLR9, NF-kappa B or I kappa B alpha markedly inhibited CpG ODN-induced IL-6 and TNF-alpha expression. Moreover, the CpG ODN-mediated increase of kappa B-luciferase activity in MDPC-23 cells was suppressed by the overexpression of dominant negative mutants of TLR9. MyD88 and I kappa B alpha, but not by the dominant negative mutant of TLR4. This result suggests a possible role for the CpG DNA-mediated immune response in odontoblasts and indicates that TLR9, MyD88 and NF-kappa B are involved in this process. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.