Flavonoids differentially regulate IFNγ‐induced ICAM‐1 expression in human keratinocytes: molecular mechanisms of action

FEBS Letters

Packer, Lester²  Roy, Sashwati³  Ichihashi, Masamitsu⁴  Shirakawa, Toshiro¹  Sen, Chandan K.³  Bito, Toshinori²  Gotoh, Akinobu¹  Ueda, Masato⁴ 

[1] Department of Urology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho Chuoku, Kobe 650-0017, Japan;Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA;Laboratory of Molecular Medicine, Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH 43210, USA;Department of Dermatology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho Chuoku, Kobe 650-0017, Japan

关键词: Cell adhesion;    Taxifolin;    Tyrosine kinase activation;    Signal transducers and activators of transcription 1;    ICAM-1;    intercellular adhesion molecule-1;    IFNγ;    interferon γ;    JAK1;    Janus kinase 1;    STAT1;    signal transducers and activators of transcription 1;   

DOI  :  10.1016/S0014-5793(02)02810-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 γ (IFNγ)-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 IFNγ-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.

【 授权许可】

Unknown