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査読

37 被引用数 (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
出版ステータスPublished - 2010 10月

ASJC Scopus subject areas

  • 免疫学
  • 薬理学


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