title: The flavone eupatilin inhibits eotaxin expression in an NF-κB-dependent and STAT6-independent manner.
abstract: The CC chemokine eotaxin contributes to epithelium-induced inflammation in airway diseases such as asthma. Eupatilin (5,7-dihydroxy-3',4',6'-trimethoxyflavone), a bioactive component of Artemisia asiatica Nakai (Asteraceae), is reported to inhibit the adhesion of eosinophils to bronchial epithelial cells. However, little is known about the molecular mechanism of eupatilin-induced attenuation of bronchial epithelium-induced inflammation. In this study, we investigated the effect of eupatilin on expression of eotaxin-1 (CCL11), a potent chemoattractant for eosinophils. Eupatilin significantly inhibited eotaxin expression in bronchial epithelial cells stimulated with TNF-α, while NF-κB and IκBα kinase (IKK) activities declined concurrently. Eupatilin also inhibited mitogen-activated protein kinase (MAPK) activity; however, all of these anti-inflammatory activities were reversed by MAPK overexpression. In contrast, eupatilin did not affect the signal transducer and activator of transcription 6 (STAT6) signalling in bronchial epithelial cells stimulated with IL-4. Furthermore, eupatilin significantly attenuated TNF-α-induced eosinophil migration. These results suggest that the eupatilin inhibits the signalling of MAPK, IKK, NF-κB and eotaxin-1 in bronchial epithelial cells, leading to inhibition of eosinophil migration.
authors.affiliation: Department of Microbiology and Department of Biomedical Science, Hanyang University College of Medicine and Hanyang University Graduate School of Biomedical Science and Engineering, Seoul, South Korea.
authors.forename: J I
authors.initials: JI
authors.lastname: Jeon
authors.forename: S H
authors.initials: SH
authors.lastname: Ko
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Kim
authors.forename: S M
authors.initials: SM
authors.lastname: Choi
authors.forename: K K
authors.initials: KK
authors.lastname: Kang
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: H J
authors.initials: HJ
authors.lastname: Yoon
authors.forename: J M
authors.initials: JM
authors.lastname: Kim
mesh_terms: D001249:Asthma; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D054413:Chemokine CCL11 / Q000096:biosynthesis*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004804:Eosinophils / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D015847:Interleukin-4 / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D020545:Respiratory Mucosa / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; C508598:IL4 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; C045325:eupatilin; D051550:I-kappa B Kinase; D020928:Mitogen-Activated Protein Kinases