Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/28/2008
Publication Date: 5/25/2008
Citation: Cao, H., Urban Jr, J.F., Anderson, R.A. 2008. Cinnamon polyphenol extract affects immune responses by regulating anti- and proinflammatory and glucose transporter gene expression in mouse macrophages. Journal of Nutrition. 138(5):833-840. Interpretive Summary: Diet has been shown to play an important role in the prevention of inflammation-related diseases, such as arthritis, obesity, and type 2 diabetes. The diets commonly consumed in the United States and other developed countries appear to increase the incidence of these diseases. For the majority of the world population, drug treatment for these diseases is not feasible and alternative treatments need to be evaluated. Previous studies suggest that cinnamon and green tea extracts induce gene expression of tristetraprolin (TTP), a regulatory protein with anti-inflammatory function. This study compared the effects of aqueous extracts of cinnamon (CE), insulin, and a bacterial endotoxin on TTP family and pro-inflammatory cytokine gene expression in macrophages. Our results demonstrate that CE increases anti-inflammatory TTP gene expression more rapidly than pro-inflammatory cytokines, and support the anti-inflammatory effects of CE during the initial immune responses. These findings should be of interest to scientists, medical personnel, and the lay public.
Technical Abstract: Tristetraprolin (TTP/TIS11/ZFP36) family proteins have anti-inflammatory effects by polyphenoldestabilizing pro-inflammatory mRNAs. TTP expression is induced by insulin and cinnamon extract (CPE) in adipocytes, by lipopolysaccharide (LPS) in macrophages, and by green tea extract in rats. This study compared the effects of CPE, insulin, and LPS on TTP family and pro-inflammatory cytokine gene expression in RAW264.7 cells. Real-time PCR showed that TTP mRNA levels were 2.2-, 0.2-, and 8-fold of TIS11B, TIS11D, ZFP36L3, and its levels were 0.5-, 33-, 1.3-, 6-, 50-, 500-, and 3000-fold of HuR, VEGFA, VEGFB, TNF, COX2, GM-CSF, and IL6 in unstimulated cells, respectively. CPE (100 ug/ml) increased TTP mRNA levels within 30 min and, after 4 h, increased TTP, TNF, COX2, and IL6 mRNA levels up to 2-, 6-, 3-, and 3-fold, respectively. LPS (0.1 ug/ml, 4 h) increased TTP, TNF, GM-CSF, COX2, and IL6 mRNA levels by 39-, 48-, 1256-, 532-, and 1868-fold, respectively. Insulin (100 nM, 0.5-4 h) did not exhibit significant effects on the expression of these genes. Immunoblotting showed that CPE increased TTP protein levels, but to a much less extent than LPS. These results demonstrate that CPE increases anti-inflammatory TTP gene expression more rapidly than pro-inflammatory cytokines, and support the anti-inflammatory effects of CPE during initial immune responses.