Effect of Toll-like receptor 4 inhibitor on LPS-induced lung injury.
Inflamm Res
; 59(10): 837-45, 2010 Oct.
Article
en En
| MEDLINE
| ID: mdl-20387088
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 ANDMETHODS:
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.CONCLUSION:
TAK-242 may be a promising therapeutic agent for ALI, especially injuries associated with pneumonia caused by Gram-negative bacteria.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sulfonamidas
/
Lipopolisacáridos
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Receptor Toll-Like 4
/
Lesión Pulmonar Aguda
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Inflamm Res
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
PATOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Japón