Discovery of a novel TLR2 signaling inhibitor with anti-viral activity.
Discovery of a novel TLR2 signaling inhibitor with anti-viral activity.
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DOI：
10.1016/j.antiviral.2010.06.011
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发表时间：
2010-09
影响因子：
7.6
通讯作者：
Finberg, Robert W.
中科院分区：
文献类型：
--
作者：
Zhou, Shenghua;Cerny, Anna M.;Bowen, Glennice;Chan, Melvin;Knipe, David M.;Kurt-Jones, Evelyn A.;Finberg, Robert W.
阻断Toll样受体（TLR）介导的炎症反应代表了抗炎治疗发展的新途径。在本研究中，我们使用稳定表达TLR 2、CD 14和NF-κ B驱动的荧光素酶报告基因的敏感细胞系，从小分子化合物库中筛选TLR 2介导的炎症抑制剂。淋巴细胞性脉络丛脑膜炎病毒（LCMV）被用作病毒模型。该沙粒病毒激活TLR 2/CD 14依赖性NF-κB信号通路。我们从101306种化合物中鉴定出10种潜在的抗炎化合物。我们进一步评价了这些阳性化合物中的一种，E567。我们证明了化合物E567有效地抑制人和小鼠细胞培养物中LCMV和单纯疱疹病毒1（HSV-1）诱导的细胞因子应答。我们还证明了E567抑制小鼠中的细胞因子应答。值得注意的是，E567还能够抑制小鼠中的LCMV复制。这是开发用于治疗病毒性疾病的药物的新模式。
Blockade of Toll-like receptor (TLR)-mediated inflammatory responses represents a new approach in the development of anti-inflammation therapeutics. In the present study, we have screened for TLR2-mediated inflammation inhibitors from a small molecule compound library using a sensitive cell line stably expressing TLR2, CD14, and an NF-κB-driven-luciferase reporter gene. Lymphocytic choriomeningitis virus (LCMV) was used as a virus model. This arenavirus activates a TLR2/CD14-dependent NF-κB signaling pathway. We have identified 10 potential anti-inflammatory compounds out of 101306 compounds. We further evaluated 1 of these positive compounds, E567. We demonstrated that compound E567 efficiently inhibits both LCMV and Herpes simplex virus 1 (HSV-1) induced cytokine responses in both human and mouse cell cultures. We also demonstrated that E567 inhibits cytokine responses in the mouse. Remarkably, E567 is also capable of inhibiting LCMV replication in mice. This is a new model for developing drugs for use in treating viral illnesses.
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Toll样受体（TLR）3对病毒诱导的急性肺炎的有害贡献。
影响因子：
6.7
作者：
Le Goffic, Ronan;Balloy, Viviane;Lagranderie, Micheline;Alexopoulou, Lena;Escriou, Nicolas;Flavell, Richard;Chignard, Michel;Si-Tahar, Mustapha
通讯作者：
Si-Tahar, Mustapha
影响因子：
3.7
作者：
Gowen BB;Smee DF;Wong MH;Hall JO;Jung KH;Bailey KW;Stevens JR;Furuta Y;Morrey JD
通讯作者：
Morrey JD
影响因子：
7.3
作者：
Seyberth, T;Voss, S;Jung, G
通讯作者：
Jung, G
影响因子：
5.4
作者：
Zhou, SH;Kurt-Jones, EA;Finberg, RW
通讯作者：
Finberg, RW
影响因子：
5.4
作者：
Murawski, Matthew R.;Bowen, Glennice N.;Finberg, Robert W.
通讯作者：
Finberg, Robert W.