期刊
CRITICAL CARE MEDICINE
卷 32, 期 10, 页码 2097-2103出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.CCM.0000142661.73633.15
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资金
- NIGMS NIH HHS [R01GM061723, T32GM08478] Funding Source: Medline
Objective: Tea has been around for centuries, and its medicinal properties have been purported in the literature but never fully confirmed. Interleukin-8 is a principle neutrophil chemoattractant and activator in humans. We determined the effects of theaflavin, a black tea-derived polyphenol, on tumor necrosis factor-alpha-mediated expression of the interleukin-8 gene in A549 cells. Design: Prospective laboratory study. Setting: University laboratory. Subjects: A549 cells. Interventions: A549 cells were exposed to varying concentrations of theaflavin and analyzed for tumor necrosis factor-alpha-mediated interleukin-8 gene expression. Measurements and Main Results. Theaflavin inhibited tumor necrosis factor-alpha-mediated interleukin-8 gene expression, as measured by luciferase assay and Northern blot analysis, at concentrations of 10 and 30 mug/mL. This effect appears to primarily involve inhibition of interleukin-8 transcription because theaflavin inhibited tumor necrosis factor-alpha-mediated activation of the interleukin-8 promoter in cells transiently transfected with an interleukin-8 promoter- luc iferase reporter plasmid. In addition, theaflavin inhibited tumor necrosis factor-alpha-mediated activation of IKB kinase and subsequent activation of the IKB-alpha/nuclear factor-KB pathway. Theaflavin also significantly reduced tumor necrosis factor-alpha-mediated DNA binding of activator protein-1. Conclusions. We conclude that theaflavin is a potent inhibitor of interleukin-8 gene expression in vitro. The proximal mechanism of this effect involves, in part, inhibition of IKB kinase activation and activator protein-1 pathway.
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