Beta-Naphthoflavone protects from peritonitis by reducing TNF-alpha-induced endothelial cell activation. (December 2015)

• Record Type: Journal Article
• Authors: Hsu, Sheng-Yao; Liou, Je-Wen; Cheng, Tsung-Lin; Peng, Shih-Yi; Lin, Chi-Chen; Chu, Yuan-Yuan; Luo, Wei-Cheng; Huang, Zheng-Kai; Jiang, Shinn-Jong
• Is Part Of: Pharmacological research. Volume 102(2015:Dec.)
• Page Start: 192
• Page End: 199
• Publication Date: 2015-12
• Subjects: β-NF β-Naphthoflavone -- Egr-1 early growth response gene-1 -- ERK extracellular signal-regulated kinase -- HUVECs human umbilical vein endothelial cells -- ICAM-1 intracellular adhesion molecule-1 -- LPS lipopolysaccharide -- MCP-1 monocyte chemotactic protein-1 -- NF-κB nuclear factor-κB -- TNF-α tumor necrosis factor -- VCAM-1 vascular cell adhesion molecule-1; Endothelial cells -- β-Naphthoflavone -- Inflammation -- Adhesion molecule; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2015.10.001
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: 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 p67 phox, 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.