|Kari, Frank - DHHS-NIH-NIEHS-LN, NC|
|Coves, Sara - UNILEVER, FRANCE|
|Roussel, Anne - J.FOURIER U.,NVMC FRANCE|
|Polyphenol Technologies Corporation|
Submitted to: Journal of Inflammation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 5, 2007
Publication Date: January 5, 2007
Citation: Cao, H., Kelly, M.A., Kari, F., Dawson, H.D., Urban Jr, J.F., Coves, S., Roussel, A.M., Anderson, R.A. 2007. Green tea increases the anti-inflammatory tristetraprolin and decreases the pro-inflammatory tumor necrosis factor mRNA levels in rats. Journal of Inflammation. 4(1):1-12. Interpretive Summary: Tea is the most popular beverage worldwide. Recent studies indicate that tea has a wide range of effects on human health. It has been reported that tea reduces cancer risk in humans, reduces carcinogen-induced malignancies in animals, inhibits tumor formation and tumor growth, and is a potential neuroprotective agent in Alzheimer’s and Parkinson’s diseases. A number of studies have indicated that green tea has antiinflammatory properties. We hypothesized that a unique antiinflammatory protein called tristetraprolin, that decreases some mRNAs involved in inflammatory responses, might be involved in tea’s antiinflammatory effects. In this study, we explored the relationship between green tea and the messenger ribonucleic acid (mRNA, whose sequence determineds protein sequence) levels of some proinflammatory and antiinflammatory genes in the liver and muscle of rats fed a high sugar diet to decrease the effectiveness of insulin. We demonstrated that a low dose of green tea (1 g/kg diet) significantly increased the mRNA levels of the antiinflammatory protein, tristetraprolin, and decreased those of the proinflammatory proteins in both liver and muscle. To our knowledge, this is the first report to show that a plant nutritional product such as green tea can modulate antiinflammatory mRNA levels in an animal and the results provide a novel mechanism for green tea’s antiinflammatory properties. These results suggest that drinking adequate amounts of green tea may play a role in the prevention and/or treatment of inflammation-related diseases.
Technical Abstract: Tristetraprolin (TTP) family proteins have antiinflammatory activity by binding to and destabilizing proinflammatory mRNAs such as TNF mRNA, and represent a potential therapeutic target for inflammation-related diseases. Tea has antiinflammatory properties but the molecular mechanism has not been elucidated. Quantitative real-time PCR was used to investigate the effects of green tea on the expression of TTP family genes (Zfp36, Zfp36l1, Zfp36l2, Zfp36l3), proinflammatory genes (TNF, GM-CSF, COX-2), and HuR, VEGFa, and VEGFb genes in rats fed a high-fructose diet known to induce insulin resistance. TTP and Zfp36L1 mRNAs were the major forms in both liver and skeletal muscle. TTP, Zfp36L1, and Zfp36L2 mRNA levels were more abundant in the liver than those in the muscle. GM-CSF and Zfp36L3 mRNAs were undetectable in either tissue. Tea (1 g solid/kg diet) increased TTP mRNA levels by 50-140% but TNF mRNA level decreased by 30% in both tissues, and COX-2 mRNA levels decreased by 40% in the muscle. Tea at (2 g solid/kg diet) increased HuR mRNA levels by 40% in the liver but did not affect any of the other mRNA levels in liver or muscle. These results show that tea could modulate TTP mRNA levels in animals and suggest that a posttranscriptional mechanism through TTP could partially account for tea’s antiinflammatory properties.