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

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)837-845
Number of pages9
JournalInflammation Research
Volume59
Issue number10
DOIs
Publication statusPublished - 2010 Oct

Fingerprint

Toll-Like Receptor 4
Lung Injury
Lipopolysaccharides
Acute Lung Injury
Lung
Permeability
Lipopeptides
Neutrophil Activation
DNA
Bronchoalveolar Lavage Fluid
Gram-Negative Bacteria
Inbred C57BL Mouse
Peroxidase
Signal Transduction
Pneumonia
Cell Count
ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate
Cytokines
Wounds and Injuries

Keywords

  • Acute lung injury
  • Endotoxin
  • NF-κB
  • Rodent
  • Toll-like receptor 4

ASJC Scopus subject areas

  • Pharmacology
  • Immunology

Cite this

Seki, H., Tasaka, S., Fukunaga, K., Shiraishi, Y., Moriyama, K., Miyamoto, K., ... 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

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

In: Inflammation Research, Vol. 59, No. 10, 10.2010, p. 837-845.

Research output: Contribution to journalArticle

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, vol. 59, no. 10, pp. 837-845. https://doi.org/10.1007/s00011-010-0195-3
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. / Effect of toll-like receptor 4 inhibitor on LPS-induced lung injury. In: Inflammation Research. 2010 ; Vol. 59, No. 10. pp. 837-845.
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