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

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 a...

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Veröffentlicht in:Inflammation research 2010-10, Vol.59 (10), p.837-845
Hauptverfasser: Seki, Hiroyuki, Tasaka, Sadatomo, Fukunaga, Koichi, Shiraishi, Yoshiki, Moriyama, Kiyoshi, Miyamoto, Keisuke, Nakano, Yasushi, Matsunaga, Naoko, Takashima, Katsunori, Matsumoto, Tatsumi, Ii, Masayuki, Ishizaka, Akitoshi, Takeda, Junzo
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Sprache:eng
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Zusammenfassung: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.
ISSN:1023-3830
1420-908X
DOI:10.1007/s00011-010-0195-3