title: beta-Naphthoflavone protects from peritonitis by reducing TNF-alpha-induced endothelial cell activation.
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-1 and 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.
authors.affiliation: Department ofOphthalmology,ChinaMedicalUniversity-AnNan Hospital,Tainan,Taiwan.; School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Sheng-Yao
authors.initials: SY
authors.lastname: Hsu
authors.affiliation: Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Je-Wen
authors.initials: JW
authors.lastname: Liou
authors.affiliation: Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Tsung-Lin
authors.initials: TL
authors.lastname: Cheng
authors.affiliation: Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Shih-Yi
authors.initials: SY
authors.lastname: Peng
authors.affiliation: Institute of Biomedical Sciences, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Postgraduate program in Biochemistry, School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Chu
authors.affiliation: Master program in Microbiology, Immunology and Biochemistry, School of Medicine Master Thesis, Tzu Chi University, Hualien, Taiwan.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Luo
authors.affiliation: Bachelor in Department of Molecular Biology and Human Genetics, College of Life Sciences, Tzu Chi University, Hualien, Taiwan.
authors.forename: Zheng-Kai
authors.initials: ZK
authors.lastname: Huang
authors.affiliation: Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien, Taiwan. Electronic address: sjjiang@mail.tcu.edu.tw.
authors.forename: Shinn-Jong
authors.initials: SJ
authors.lastname: Jiang
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010538:Peritonitis / Q000188:drug therapy* / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019324:beta-Naphthoflavone / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D020011:Protective Agents; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D019324:beta-Naphthoflavone
keywords: Adhesion molecule; Endothelial cells; Inflammation; β-Naphthoflavone