In vivo TLR9 inhibition attenuates CpG-induced myocardial dysfunction.
In vivo TLR9 inhibition attenuates CpG-induced myocardial dysfunction.
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DOI：
10.1155/2013/217297
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发表时间：
2013
影响因子：
4.6
通讯作者：
Knuefermann P
中科院分区：
文献类型：
--
作者：
Boehm O;Markowski P;van der Giet M;Gielen V;Kokalova A;Brill C;Hoeft A;Baumgarten G;Meyer R;Knuefermann P
toll样受体9 （toll-like receptor 9, TLR9）是一种细菌DNA受体，在脓毒性心脏抑制中的作用尚未在体内得到澄清。因此，本研究的目的是测试可能的TLR9抑制剂（h154 -硫酸盐、irs954 -硫酸盐和氯喹）在CpG寡聚脱氧核苷酸（ODN-）依赖性全身炎症小鼠模型中保护心血管系统的能力。在C57BL/6野生型（WT）和TLR9缺陷型（TLR9- d）小鼠中应用TLR9激动剂1668-硫酸盐诱导脓毒症。刺激后30分钟，静脉注射TLR9拮抗剂。刺激后18小时监测生存情况。在1668-硫代酸刺激后2 h和6 h分析心肌炎症介质mRNA表达，并在后期监测血流动力学参数。在WT动物中，1668-硫酸盐刺激引起严重的脓毒症样状态，体温显著下降，死亡率显著增加。此外，随着脓毒性心力衰竭的发展，心脏中炎症介质呈时间依赖性增加。这些作用在TLR9-D小鼠中未观察到。通过抑制性ODN h154 -硫酸盐抑制TLR9可显著改善心脏炎症，保存心功能，提高生存率。这种抑制性ODN是被试物质中最有效的抑制剂。
The involvement of toll-like receptor 9 (TLR9), a receptor for bacterial DNA, in septic cardiac depression has not been clarified in vivo. Thus, the aim of the study was to test possible TLR9 inhibitors (H154-thioate, IRS954-thioate, and chloroquine) for their ability to protect the cardiovascular system in a murine model of CpG oligodeoxynucleotide- (ODN-) dependent systemic inflammation. Sepsis was induced by i.p. application of the TLR9 agonist 1668-thioate in C57BL/6 wild type (WT) and TLR9-deficient (TLR9-D) mice. Thirty minutes after stimulation TLR9 antagonists were applied i.v. Survival was monitored up to 18 h after stimulation. Cardiac mRNA expression of inflammatory mediators was analyzed 2 h and 6 h after stimulation with 1668-thioate and hemodynamic parameters were monitored at the later time point. Stimulation with 1668-thioate induced a severe sepsis-like state with significant drop of body temperature and significantly increased mortality in WT animals. Additionally, there was a time-dependent increase of inflammatory mediators in the heart accompanied by development of septic heart failure. These effects were not observed in TLR9-D mice. Inhibition of TLR9 by the suppressive ODN H154-thioate significantly ameliorated cardiac inflammation, preserved cardiac function, and improved survival. This suppressive ODN was the most efficient inhibitor of the tested substances.
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影响因子：
3.7
作者：
Ehrentraut SF;Dörr A;Ehrentraut H;Lohner R;Lee SH;Hoeft A;Baumgarten G;Knuefermann P;Boehm O;Meyer R
通讯作者：
Meyer R
影响因子：
5.4
作者：
Sparwasser, T;Miethke, T;Wagner, H
通讯作者：
Wagner, H
影响因子：
4.4
作者：
Shirota, H;Gursel, I;Klinman, DM
通讯作者：
Klinman, DM
影响因子：
64.8
作者：
KRIEG, AM;YI, AK;KLINMAN, DM
通讯作者：
KLINMAN, DM
影响因子：
10.8
作者：
Knuefermann, Pascal;Schwederski, Markus;Meyer, Rainer
通讯作者：
Meyer, Rainer