MDP up-regulates the gene expression of type I interferons in human aortic endothelial cells.
MDP up-regulates the gene expression of type I interferons in human aortic endothelial cells.
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MDP 上调人主动脉内皮细胞中 I 型干扰素的基因表达。
DOI：
10.3390/molecules17043599
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发表时间：
2012-03-23
期刊：
影响因子：
--
通讯作者：
Hu J
中科院分区：
文献类型：
--
作者：
Lv Q;Yang M;Liu X;Zhou L;Xiao Z;Chen X;Chen M;Xie X;Hu J
胞壁酰二肽（MDP）是肽聚糖免疫佐剂活性的最小必需结构，由细胞内核结合寡聚化结构域2（NOD 2）识别。在这里，我们获得的证据表明，治疗的人主动脉内皮细胞（HAECs）与MDP上调基因表达的I型干扰素的剂量和时间依赖性的方式。MDP还上调NOD 2受体的表达，表明MDP可能诱导正反馈反应。MDP刺激HAECs不表达TNFα，TNFα中和抗体不降低MDP诱导的IFN产生，因此IFN的上调不依赖于TNFα信号。RT-PCR结果显示HAECs表达干扰素调节因子（IRF）1、2、3、9的基因转录本。Western blot结果显示MDP诱导IRF 3磷酸化。这些结果表明，MDP通过激活IRF 3信号通路诱导干扰素基因转录的上调。同时，MDP诱导促炎细胞因子的基因表达，包括IL-1β、IL-8和MCP-1。这些结果表明，HAECs可能在抗感染免疫应答和诱导天然免疫中发挥作用。
Muramyldipeptide (MDP), the minimum essential structure responsible for the immuno-adjuvant activity of peptidoglycan, is recognized by intracellular nuclear-binding oligomerization domain 2 (NOD2). Here, we obtained evidence that the treatment of human aortic endothelial cells (HAECs) with MDP up-regulated the gene expression of type I interferons in a dose- and time-dependent manner. MDP also up-regulated the expression of the receptor NOD2, suggesting that MDP may induce a positive feedback response. The up-regulation of interferons was not dependent on the TNFα signaling, as HAECs did not express TNFα with the stimulation of MDP, and TNFα neutralizing antibody did not decrease the induction of IFNs induced by MDP. RT-PCR results showed that HAECs expressed the gene transcripts of interferon regulatory factor (IRF) 1, 2, 3, 9. The western blot results showed that MDP induced the phosphorylation of IRF3. These results suggested that MDP induced the up-regulation of gene transcript of interferons through the activation of IRF3 signaling pathway. Meanwhile, MDP induced the gene expression of pro-inflammatory cytokines, including IL-1β, IL-8, and MCP-1. Taken together, these results suggested that HAECs may play roles in the anti-infection immune response and in the induction of innate immunity.
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