title: Luteolin, a flavonoid, inhibits AP-1 activation by basophils.
abstract: Flavonoids including luteolin, apigenin, and fisetin are inhibitors of IL-4 synthesis and CD40 ligand expression by basophils. This study was done to search for compounds with greater inhibitory activity of IL-4 expression and to clarify the molecular mechanisms through which flavonoids inhibit their expression. Of the 37 flavonoids and related compounds examined, ayanin, luteolin, and apigenin were the strongest inhibitors of IL-4 production by purified basophils in response to anti-IgE antibody plus IL-3. Luteolin did not suppress Syk or Lyn phosphorylation in basophils, nor did suppress p54/46 SAPK/JNK, p38 MAPK, and p44/42 MAPK activation by a basophilic cell line, KU812 cells, stimulated with A23187 and PMA. However, luteolin did inhibit phosphorylation of c-Jun and DNA binding activity of AP-1 in nuclear lysates from stimulated KU812 cells. These results provide a fundamental structure of flavonoids for IL-4 inhibition and demonstrate a novel action of flavonoids that suppresses the activation of AP-1.
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Medical School, Osaka 565-0871, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Hirano
authors.forename: Shinji
authors.initials: S
authors.lastname: Higa
authors.forename: Junsuke
authors.initials: J
authors.lastname: Arimitsu
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Naka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogata
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Shima
authors.forename: Minoru
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Tomoki
authors.initials: T
authors.lastname: Yamadori
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Ohkawara
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kuwabara
authors.forename: Mari
authors.initials: M
authors.lastname: Kawai
authors.forename: Hisashi
authors.initials: H
authors.lastname: Matsuda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Maezaki
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
authors.forename: Toshio
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D001491:Basophils / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism*; D047311:Luteolin / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D018808:Transcription Factor AP-1; D015847:Interleukin-4; D047311:Luteolin