title: Effect of Toll-like receptor 4 inhibitor on LPS-induced lung injury.
abstract: OBJECTIVE
  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).
  
  
  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-kappaB (NF-kappaB) 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-kappaB DNA-binding activity induced by the LPS challenge. In contrast, TAK-242 did not suppress inflammatory changes induced by Pam3CSK4.
  
  
  CONCLUSIONS
  TAK-242 may be a promising therapeutic agent for ALI, especially injuries associated with pneumonia caused by Gram-negative bacteria.
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Seki
authors.forename: Sadatomo
authors.initials: S
authors.lastname: Tasaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shiraishi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Moriyama
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakano
authors.forename: Naoko
authors.initials: N
authors.lastname: Matsunaga
authors.forename: Katsunori
authors.initials: K
authors.lastname: Takashima
authors.forename: Tatsumi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ii
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
authors.forename: Junzo
authors.initials: J
authors.lastname: Takeda
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013449:Sulfonamides / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013449:Sulfonamides; D051197:Toll-Like Receptor 4; C507035:ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate
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