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 |
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Rok vydání: | 2015 |
Předmět: |
Adhesion molecule
MAP Kinase Signaling System Endothelial cells Anti-Inflammatory Agents Peritonitis Protective Agents Proinflammatory cytokine chemistry.chemical_compound beta-Naphthoflavone Cell Adhesion Human Umbilical Vein Endothelial Cells medicine Humans VCAM-1 Cell adhesion Cells Cultured Inflammation Pharmacology ICAM-1 Interleukin-6 Tumor Necrosis Factor-alpha Cell adhesion molecule Monocyte Transcription Factor RelA β-Naphthoflavone Cell biology Endothelial stem cell medicine.anatomical_structure chemistry Tumor necrosis factor alpha Reactive Oxygen Species Signal Transduction |
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 |
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