Involvement of ERK, p38 and NF-κB signal transduction in regulation of TLR2, TLR4 and TLR9 gene expression induced by lipopolysaccharide in mouse dendritic cells
Involvement of ERK, p38 and NF-κB signal transduction in regulation of TLR2, TLR4 and TLR9 gene expression induced by lipopolysaccharide in mouse dendritic cells
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DOI：
10.1046/j.1365-2567.2002.01401.x
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发表时间：
2002-05-01
期刊：
影响因子：
6.4
通讯作者：
Cao, XT
中科院分区：
文献类型：
--
作者：
An, HZ;Yu, YH;Cao, XT
Toll 样受体 (TLR) 是能够识别病原体相关分子模式 (PAMP) 的前哨受体，例如脂多糖 (LPS) 和含 CpG 的寡核苷酸 (CpG ODN)。 TLR2 和 TLR4 分别是革兰氏阳性和革兰氏阴性细菌细胞壁成分的主要受体。 TLR9 对于 CpG 信号传导是必需的。 LPS 或 CpG ODN 可以激活未成熟的树突状细胞 (DC) 并诱导 DC 成熟，其特征是产生细胞因子、上调共刺激分子以及增强激活 T 细胞的能力。然而，对于小鼠 DC 中 TLR 基因表达的调控知之甚少。在本研究中，我们研究了LPS对小鼠未成熟DC中TLR2、TLR4和TLR9基因表达的调节。 LPS 刺激后 TLR2、TLR4 和 TLR9 mRNA 上调。 TLR9 表达的上调与 LPS 加 CpG ODN 诱导的肿瘤坏死因子-α 的产生显着增加同时发生。抑制细胞外信号相关激酶和NF-κB激活可抑制TLR2、TLR4和TLR9 mRNA表达的上调，而抑制p38激酶可阻止TLR2和TLR4 mRNA表达的上调，但增强TLR9表达的上调。这些结果表明，小鼠未成熟DC中TLR2、TLR4和TLR9基因表达受到LPS的不同调节。 LPS 上调 TLR2、TLR4 和 TLR9 表达可能会促进 DC 对细菌的整体反应，并有助于解释 LPS 和其他细菌产物在诱导细胞因子产生中的协同作用。
Toll-like receptors (TLR) are sentinel receptors capable of recognizing pathogen-associated molecule patterns (PAMP) such as lipopolysaccharide (LPS) and CpG-containing oligonucleotides (CpG ODN). TLR2 and TLR4 are major receptors for Gram-positive and Gram-negative bacterial cell wall components, respectively. TLR9 is necessary for CpG signalling. LPS or CpG ODN can activate immature dendritic cells (DC) and induce DC maturation characterized by production of cytokines, up-regulation of co-stimulatory molecules, and increased ability to activate T cells. However, little is known regarding the regulation of TLR gene expression in mouse DC. In this study, we investigated the regulation of TLR2, TLR4 and TLR9 gene expression by LPS in murine immature DC. TLR2, TLR4 and TLR9 mRNA were up-regulated following LPS stimulation. The up-regulation of TLR9 expression coincided with significantly increased production of tumour necrosis factor-alpha induced by LPS plus CpG ODN. While inhibition of extracellular signal-related kinase and NF-kappaB activation suppressed the up-regulation of the expression of TLR2, TLR4 and TLR9 mRNA, inhibition of p38 kinase prevented the up-regulation of TLR2 and TLR4 mRNA expression but enhanced the up-regulation of TLR9 expression. These results demonstrated that TLR2, TLR4 and TLR9 gene expression was differently regulated by LPS in mouse immature DC. Up-regulation of TLR2, TLR4 and TLR9 expression by LPS might promote the overall responses of DC to bacteria and help to explain the synergy between LPS and other bacterial products in the induction of cytokine production.