beta-Naphthoflavone protects from peritonitis by reducing TNF-alpha-induced endothelial cell activation

Autor: Tsung Lin Cheng, Shinn Jong Jiang, Sheng-Yao Hsu, Zheng-Kai Huang, Chi-Chen Lin, Wei-Cheng Luo, Yuan-Yuan Chu, Shih-Yi Peng, Je-Wen Liou
Rok vydání: 2015
Předmět:
Zdroj: Pharmacological Research. 102:192-199
ISSN: 1043-6618
DOI: 10.1016/j.phrs.2015.10.001
Popis: β-Naphthoflavone (β-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 β-NF in human microvascular endothelial cells treated with tumor necrosis factor-alpha (TNF-α). Pretreatment with β-NF significantly inhibited TNF-α-induced intracellular reactive oxygen species, translocation of p67phox, and TNF-α-induced monocyte binding and transmigration. In addition, β-NF significantly inhibited TNF-α-induced ICAM-1and VCAM-1 expression. The mRNA expression levels of the inflammatory cytokines TNF-α and IL-6 were reduced by β-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 β-NF treatment. Our findings show that β-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 β-NF might prevent TNF-α-induced inflammation.
Databáze: OpenAIRE