Effect of Toll-like receptor 4 inhibitor on LPS-induced lung injury
Effect of Toll-like receptor 4 inhibitor on LPS-induced lung injury
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DOI：
10.1007/s00011-010-0195-3
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发表时间：
2010-04
影响因子：
6.7
通讯作者：
H. Seki;S. Tasaka;K. Fukunaga;Y. Shiraishi;Kiyoshi Moriyama;K. Miyamoto;Yasushi Nakano;N. Matsunaga;K. Takashima;Tatsumi Matsumoto;Masayuki Ii;A. Ishizaka;J. Takeda
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文献类型：
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作者：
H. Seki;S. Tasaka;K. Fukunaga;Y. Shiraishi;Kiyoshi Moriyama;K. Miyamoto;Yasushi Nakano;N. Matsunaga;K. Takashima;Tatsumi Matsumoto;Masayuki Ii;A. Ishizaka;J. Takeda
目的与设计toll样受体4 （TLR4）在脂多糖（LPS）的识别和炎症级联的激活中起重要作用。在本研究中，我们评估了选择性TLR4信号转导抑制剂TAK-242对急性肺损伤（ALI）的作用。材料和方法在气管内给药LPS或Pam3CSK4（一种合成的脂肽）前15分钟，用TAK-242静脉治疗sc57bl /6J小鼠。攻毒6小时后，取支气管肺泡灌洗液进行细胞计数和细胞因子和髓过氧化物酶水平的测定。肺通透性及核因子-κB (NF-κB) DNA结合活性测定。结果stak -242能有效降低LPS刺激引起的肺中性粒细胞的聚集和活化、肺通透性、炎症介质的产生和NF-κB dna结合活性的增加。相反，TAK-242对Pam3CSK4诱导的炎症变化没有抑制作用。结论tak -242可能是治疗ALI，特别是革兰氏阴性菌引起的肺炎相关损伤的一种有前景的药物。
Objective and designToll-like receptor 4 (TLR4) plays important roles in the recognition of lipopolysaccharide (LPS) and the activation of inflammatory cascade. In this study, we evaluated the effect of TAK-242, a selective TLR4 signal transduction inhibitor, on acute lung injury (ALI).Materials and methodsC57BL/6J mice were intravenously treated with TAK-242 15 min before the intratracheal administration of LPS or Pam3CSK4, a synthetic lipopeptide. Six hours after the challenge, bronchoalveolar lavage fluid was obtained for a differential cell count and the measurement of cytokine and myeloperoxidase levels. Lung permeability and nuclear factor-κB (NF-κB) DNA binding activity were also evaluated.ResultsTAK-242 effectively attenuated the neutrophil accumulation and activation in the lungs, the increase in lung permeability, production of inflammatory mediators, and NF-κB DNA-binding activity induced by the LPS challenge. In contrast, TAK-242 did not suppress inflammatory changes induced by Pam3CSK4.ConclusionTAK-242 may be a promising therapeutic agent for ALI, especially injuries associated with pneumonia caused by Gram-negative bacteria.