Luteolin, a flavonoid, inhibits AP-1 activation by basophils.
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.
Hirano
Toru
T
Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Medical School, Osaka 565-0871, Japan.
Higa
Shinji
S
Arimitsu
Junsuke
J
Naka
Tetsuji
T
Ogata
Atsushi
A
Shima
Yoshihito
Y
Fujimoto
Minoru
M
Yamadori
Tomoki
T
Ohkawara
Tomoharu
T
Kuwabara
Yusuke
Y
Kawai
Mari
M
Matsuda
Hisashi
H
Yoshikawa
Masayuki
M
Maezaki
Naoyoshi
N
Tanaka
Tetsuaki
T
Kawase
Ichiro
I
Tanaka
Toshio
T
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*
D005419:Flavonoids; D018808:Transcription Factor AP-1; D015847:Interleukin-4; D047311:Luteolin