Effect of toll-like receptor 4 inhibitor on LPS-induced lung injury

Hiroyuki Seki, Sadatomo Tasaka, Koichi Fukunaga, Yoshiki Shiraishi, Kiyoshi Moriyama, Keisuke Miyamoto, Yasushi Nakano, Naoko Matsunaga, Katsunori Takashima, Tatsumi Matsumoto, Masayuki Ii, Akitoshi Ishizaka, Junzo Takeda

研究成果: Article

25 引用 (Scopus)


Objective and design: Toll-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 methods: C57BL/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. Results: TAK-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. Conclusion: TAK-242 may be a promising therapeutic agent for ALI, especially injuries associated with pneumonia caused by Gram-negative bacteria.

ジャーナルInflammation Research
出版物ステータスPublished - 2010 10 1

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

フィンガープリント Effect of toll-like receptor 4 inhibitor on LPS-induced lung injury' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Seki, H., Tasaka, S., Fukunaga, K., Shiraishi, Y., Moriyama, K., Miyamoto, K., Nakano, Y., Matsunaga, N., Takashima, K., Matsumoto, T., Ii, M., Ishizaka, A., & Takeda, J. (2010). Effect of toll-like receptor 4 inhibitor on LPS-induced lung injury. Inflammation Research, 59(10), 837-845. https://doi.org/10.1007/s00011-010-0195-3