Flavonoids differentially regulate IFN gamma-induced ICAM-1 expression in human keratinocytes: molecular mechanisms of action.
The effect of plant flavonoids on intercellular adhesion molecule-1 (ICAM-1) expression in human keratinocyte was investigated. ICAM-1 is known to mediate skin inflammation. Among the flavonoids tested, taxifolin was the most potent in inhibiting interferon gamma (IFN gamma)-induced ICAM-1 protein as well as mRNA expression in human keratinocytes. Much smaller dosages of taxifolin were required in primary keratinocytes compared to HaCaT (immortalized cell) to achieve similar levels of inhibition in the inducible ICAM-1 expression. Regulation of inducible ICAM-1 expression by taxifolin was at transcriptional level by inhibiting the activation of signal transducers and activators of transcription (STAT)1 and protein tyrosine phosphorylation of Janus kinase (JAK)1 suggesting that the JAK-STAT pathway may be the molecular site of action of taxifolin. Finally, taxifolin pre-treatment also potently inhibited IFN gamma-induced ICAM-1 expression in a reconstructed human skin equivalent suggesting therapeutic potential of taxifolin in skin pathological conditions related to increased cell adhesion and inflammation.
Bito
Toshinori
T
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA. bito@med.kobe-u.ac.jp
Roy
Sashwati
S
Sen
Chandan K
CK
Shirakawa
Toshiro
T
Gotoh
Akinobu
A
Ueda
Masato
M
Ichihashi
Masamitsu
M
Packer
Lester
L
D047310:Apigenin; D002392:Catechin / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003373:Coumaric Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D019169:Jurkat Cells / Q000166:cytology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D003373:Coumaric Acids; D005419:Flavonoids; D044948:Flavonols; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D014443:Tyrosine; D047310:Apigenin; D007371:Interferon-gamma; D002392:Catechin; D011794:Quercetin; C003377:taxifolin; C004999:ferulic acid