Green tea inhibits human inducible nitric-oxide synthase expression by down-regulating signal transducer and activator of transcription-1alpha activation.
Green tea has been reported to show anti-inflammatory properties because of its inhibitory effects on the expression of several pro-inflammatory genes. Because the inducible nitricoxide synthase (iNOS) plays an important role in chronic inflammatory diseases, we have focused our attention on the regulation of iNOS expression by green tea in two different human epithelial cell lines, alveolar A549/8 and colon DLD-1 cells. With the use of electrophoretic mobility shift assays, we found a green tea-mediated down-regulation of the DNA binding activity of the transcription factor signal transducer and activator of transcription-1alpha (STAT-1alpha), but not of nuclear factor-kappaB. This down-regulation of the STAT-1alpha DNA binding was shown to result from reduced tyrosine phosphorylation of the STAT-1alpha protein and not from antioxidative effects of the green tea extract. Green tea extract inhibited human iNOS expression in a concentration-dependent manner, quantified in terms of iNOS mRNA, iNOS protein, and nitric oxide production in both cell lines. This inhibitory effect of green tea resulted from transcriptional inhibition as shown in reporter gene experiments. These data suggest that green tea extracts may be promising at least as an auxiliary anti-inflammatory principle in chronic inflammatory diseases.
Tedeschi
Elisa
E
Biochemistry Section, Department of Neuroscience and Vision, University of Verona, Verona, Italy.
Menegazzi
Marta
M
Yao
Ying
Y
Suzuki
Hisanori
H
Förstermann
Ulrich
U
Kleinert
Hartmut
H
D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D016328:NF-kappa B / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010936:Plant Extracts / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
D050832:Interferon-Stimulated Gene Factor 3; D016328:NF-kappa B; D009566:Nitrates; D010936:Plant Extracts; D012333:RNA, Messenger; D013662:Tea; D014157:Transcription Factors; C079868:gamma interferon activation factor; D004247:DNA; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III