title: 5,7-Dihydroxy-3,4,6-trimethoxyflavone inhibits intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 via the Akt and nuclear factor-κB-dependent pathway, leading to suppression of adhesion of monocytes and eosinophils to bronchial epithelial cells.
abstract: 5,7-Dihydroxy-3',4',6'-trimethoxyflavone (eupatilin), the active pharmacological ingredient from Artemisia asiatica Nakai (Asteraceae), is reported to have a variety of anti-inflammatory properties in intestinal epithelial cells. However, little information is known about the molecular mechanism of eupatilin-induced attenuation of bronchial epithelial inflammation. This study investigates the role of eupatilin in the adhesion of inflammatory cells such as monocytes and eosinophils to bronchial epithelial cells. Stimulation of a human bronchial epithelial cell line (BEAS-2B) with tumour necrosis factor-α (TNF-α) increased the expression of surface adhesion molecules, including intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), in which eupatilin significantly inhibited the expression of those adhesion molecules in a dose-dependent manner. Eupatilin suppressed the TNF-α-induced activation of IκBα and nuclear factor-κB (NF-κB) signals in BEAS-2B cells. The IκB kinase (IKK) activation was also significantly reduced in eupatilin-pre-treated BEAS-2B and primary normal human bronchial epithelial (NHBE) cells. However, eupatilin did not influence AP-1 activity in TNF-α-stimulated cells. Suppression of NF-κB signalling induced by eupatilin resulted in the inhibition of the expression of adhesion molecules and the adhesion of monocytes and eosinophils to BEAS-2B cells. Furthermore, eupatilin suppressed the phosphorylation of Akt in TNF-α-stimulated BEAS-2B and NHBE cells, leading to down-regulation of NF-κB activation and adhesion molecule expression and finally to suppression of the inflammatory cell adhesion to epithelial cells. These results suggest that eupatilin can inhibit the adhesion of inflammatory cells to bronchial epithelial cells via a signalling pathway, including activation of Akt and NF-κB, as well as expression of adhesion molecules.
authors.affiliation: Departments of Microbiology and Biomedical Science, Hanyang University College of Medicine and Hanyang University Graduate School of Biomedical Science and Engineering, Seoul, South Korea.
authors.forename: Jireh
authors.initials: J
authors.lastname: Jung
authors.forename: Su H
authors.initials: SH
authors.lastname: Ko
authors.forename: Do Y
authors.initials: do Y
authors.lastname: Yoo
authors.forename: Jin Y
authors.initials: JY
authors.lastname: Lee
authors.forename: Yeong-Jeon
authors.initials: YJ
authors.lastname: Kim
authors.forename: Seul M
authors.initials: SM
authors.lastname: Choi
authors.forename: Kyung K
authors.initials: KK
authors.lastname: Kang
authors.forename: Ho J
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Kim
authors.forename: Jeehee
authors.initials: J
authors.lastname: Youn
authors.forename: Jung M
authors.initials: JM
authors.lastname: Kim
mesh_terms: D001249:Asthma / Q000276:immunology*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002448:Cell Adhesion; D002460:Cell Line; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D020672:I-kappa B Proteins / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; C045325:eupatilin; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase