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铜绿假单胞菌 3-o-C12-HSL 分子刺激后单核细胞上 toll 样受体的表达调控。

Regulation on expression of toll-like receptors on monocytes after stimulation with the 3-o-C12-HSL molecule from Pseudomonas aeruginosa.

机构信息

Department of Neonatology, Children's Hospital, Chongqing Medical University, Chongqing, China.

出版信息

Curr Microbiol. 2012 Oct;65(4):384-9. doi: 10.1007/s00284-012-0162-z. Epub 2012 Jun 27.

DOI:10.1007/s00284-012-0162-z
PMID:22735982
Abstract

Quorum sensing (QS) is a type of cell-to-cell communication. The Pseudomonas aeruginosa QS molecule N-3-(oxododecanoyl)-L-homoserine lactone (3-o-C12-HSL) has the potential to modulate the immune system of its host. However, the mechanism of that activity is yet to be fully characterized. To be able to understand this activity, we determined whether 3-o-C12-HSL has a direct effect on the immune function and the expression of toll-like receptors (TLRs) in monocytes. Monocytes were cultured with 3-o-C12-HSL at different concentrations (0, 10, 25, 50, and 100 μmol/L) for 12 h; upon exposure to 3-o-C12-HSL, IL-12 production in monocytes was inhibited, monocyte proliferation was blocked, TLR2- and 4-mRNA expressions were reduced, and TLR5-mRNA expression was increased in a dose-dependent manner. Strikingly, 3-o-C12-HSL was able to significantly induce mRNA changes in the monocytes even at the lowest concentration (10 μmol/L, P < 0.05). Interestingly, though TLR2- and 4-protein levels were reduced, TLR5 protein expression was not changed. These findings provide a new perspective toward understanding the persistence of chronic inflammation in P. aeruginosa infections. They also suggest that TLR2, 4, and 5 may not share the same signaling pathways during monocyte activation.

摘要

群体感应(QS)是一种细胞间通讯方式。铜绿假单胞菌的 QS 分子 N-3-(氧代十二烷酰基)-L-高丝氨酸内酯(3-o-C12-HSL)有可能调节其宿主的免疫系统。然而,其活性的机制尚未完全阐明。为了能够理解这种活性,我们确定 3-o-C12-HSL 是否对单核细胞的免疫功能和 Toll 样受体(TLRs)的表达有直接影响。将单核细胞在不同浓度(0、10、25、50 和 100 μmol/L)的 3-o-C12-HSL 中培养 12 小时;暴露于 3-o-C12-HSL 后,单核细胞中 IL-12 的产生受到抑制,单核细胞增殖受到阻断,TLR2 和 TLR4-mRNA 的表达减少,TLR5-mRNA 的表达呈剂量依赖性增加。值得注意的是,即使在最低浓度(10 μmol/L,P < 0.05),3-o-C12-HSL 也能够显著诱导单核细胞中的 mRNA 变化。有趣的是,虽然 TLR2 和 TLR4 蛋白水平降低,但 TLR5 蛋白表达没有变化。这些发现为理解铜绿假单胞菌感染中慢性炎症的持续存在提供了新的视角。它们还表明 TLR2、4 和 5 在单核细胞激活过程中可能不共享相同的信号通路。

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本文引用的文献

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TLR expression on neutrophils at the pulmonary site of infection: TLR1/TLR2-mediated up-regulation of TLR5 expression in cystic fibrosis lung disease.感染肺部部位中性粒细胞上的Toll样受体(TLR)表达:Toll样受体1/2(TLR1/TLR2)介导的囊性纤维化肺病中Toll样受体5(TLR5)表达上调
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Cross-platform comparison of SYBR Green real-time PCR with TaqMan PCR, microarrays and other gene expression measurement technologies evaluated in the MicroArray Quality Control (MAQC) study.
在微阵列质量控制(MAQC)研究中对SYBR Green实时荧光定量PCR与TaqMan PCR、微阵列及其他基因表达测量技术进行的跨平台比较。
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Increased toll-like receptor (TLR) 2 and TLR4 expression in monocytes from patients with type 1 diabetes: further evidence of a proinflammatory state.1型糖尿病患者单核细胞中Toll样受体(TLR)2和TLR4表达增加:炎症前状态的进一步证据。
J Clin Endocrinol Metab. 2008 Feb;93(2):578-83. doi: 10.1210/jc.2007-2185. Epub 2007 Nov 20.
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TLR pathways and IFN-regulatory factors: to each its own.Toll样受体(TLR)信号通路与干扰素调节因子:各司其职。
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