beta-Naphthoflavone protects from peritonitis by reducing TNF-alpha-induced endothelial cell activation.
Pharmacol Res
; 102: 192-9, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26453957
ABSTRACT
ß-Naphthoflavone (ß-NF), a ligand of the aryl hydrocarbon receptor, has been shown to possess anti-oxidative properties. We investigated the anti-oxidative and anti-inflammatory potential of ß-NF in human microvascular endothelial cells treated with tumor necrosis factor-alpha (TNF-α). Pretreatment with ß-NF significantly inhibited TNF-α-induced intracellular reactive oxygen species, translocation of p67(phox), and TNF-α-induced monocyte binding and transmigration. In addition, ß-NF significantly inhibited TNF-α-induced ICAM-1 and VCAM-1 expression. The mRNA expression levels of the inflammatory cytokines TNF-α and IL-6 were reduced by ß-NF, as was the infiltration of white blood cells, in a peritonitis model. The inhibition of adhesion molecules was associated with suppressed nuclear translocation of NF-κB p65 and Akt, and suppressed phosphorylation of ERK1/2 and p38. The translocation of Egr-1, a downstream transcription factor involved in the MEK-ERK signaling pathway, was suppressed by ß-NF treatment. Our findings show that ß-NF inhibits TNF-α-induced NF-kB and ERK1/2 activation and ROS generation, thereby suppressing the expression of adhesion molecules. This results in reduced adhesion and transmigration of leukocytes in vitro and prevents the infiltration of leukocytes in a peritonitis model. Our findings also suggest that ß-NF might prevent TNF-α-induced inflammation.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peritonite
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Fator de Necrose Tumoral alfa
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Beta-Naftoflavona
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Substâncias Protetoras
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Células Endoteliais da Veia Umbilical Humana
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Pharmacol Res
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Taiwan