| Summary: | 碩士 === 國立臺灣大學 === 藥理學研究所 === 93 === The intercellular adhesion molecule-1 (ICAM-1) has been implicated in the process of inflammation. Flavonoids which are naturally occurring polyphenolic compounds with a wide distribution throughout the plant kingdom, have potent anti-inflammatory property. Pretreatment of cells with flavonols ( kaempferol and quercetin ) and flavones ( apigenin and luteolin ) inhibited the IFN-γ-stimulated ICAM-1 expression and cell invasion of NCI-H292 cells. The ICAM-1 promoter activity induced by IFN-γ was attenuated using serine 727 or tyrosine 701 mutant of STAT1, indicating the critical role of tyrosine 701 or serine 727 phosphorylation in the IFN-γ-induced ICAM-1 expression. Kaempferol and quercetin inhibited the phosphorylation of serine 727, while apigenin and luteolin inhibited that of serine 727 and tyrosine 701. The ROCK inhibitor（Y27632）, PI3K inhibitor（LY294002）and JNK inhibitor（SP600125）inhibited the phosphorylation of STAT1 serine at 727. However, activation of AKT or JNK was not induced by IFN-γ. IFN-γ-induced phosphorylation of mTOR was inhibited by LY294002 and SP600125, indicating the direct inhibition on mTOR activation by these two inhibitors. These results also suggested that IFN-γ-induced phosphorylation of serine 727 is through the activation of mTOR. Kaempferol, quercetin, apigenin and luteolin inhibited the phosphorylation of mTOR as well. In summary, the inhibitory effects of flavonoids on ICAM-1 expression are mediated by the sequential attenuation of mTOR/p70 s6kinase signaling pathways and serine 727 phosphorylation of STAT1
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