Cinnamon polyphenol extract affects immune responses by regulating anti- and proinflammatory and glucose transporter gene expression in mouse macrophages.
Tristetraprolin (TTP/zinc finger protein 36) family proteins have antiinflammatory effects by destabilizing proinflammatory mRNA. TTP expression is reduced in fats of obese people with metabolic syndrome and brains of suicide victims and is induced by insulin and cinnamon polyphenol extract (CPE) in adipocytes, by lipopolysaccharide (LPS) in macrophages, and by green tea polyphenol extract in rats. CPE was reported to improve immune function against microorganisms, but the mechanism is unknown. This study tested the hypothesis that CPE regulates immune function involving genes encoding TTP, proinflammatory cytokines, and glucose transporter (GLUT) families and compared the effects of CPE to those of insulin and LPS in mouse RAW264.7 macrophages. CPE increased TTP mRNA and protein levels, but its effects were less than LPS. CPE (100 mg/L, 0.5-4 h) increased TTP and tumor necrosis factor (TNF) mRNA levels by up to 2- and 6-fold that of the control, respectively, and the base level of TTP was 6-fold that of TNF. LPS (0.1 mg/L, 4 h) increased TTP, TNF, granulocyte-macrophage colony-stimulating factor, cyclooxgenase-2, and interleukin 6 mRNA levels by 39-1868 fold. CPE and LPS increased GLUT1 expression (the major GLUT form in macrophages) to 3- and 2-fold that of the control, respectively. Insulin (100 nmol/L, 0.5-4 h) did not exhibit major effects on the expression of these genes. CPE increased TTP expression more rapidly than those of proinflammatory cytokines and the net increases of TTP mRNA levels were larger than those of proinflammatory cytokines. These results suggest that CPE can affect immune responses by regulating anti- and proinflammatory and GLUT gene expression.
Cao
Heping
H
Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, USDA, Beltsville, MD 20705-2350, USA. heping.cao@ars.usda.gov
Urban
Joseph F
JF
Anderson
Richard A
RA
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D002460:Cell Line; D002935:Cinnamomum zeylanicum / Q000737:chemistry*; D016207:Cytokines / Q000235:genetics; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005419:Flavonoids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D051272:Glucose Transporter Type 1 / Q000235:genetics; D007109:Immunity / Q000187:drug effects*; D007249:Inflammation / Q000235:genetics*; D007328:Insulin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000235:genetics; D051816:Tristetraprolin / Q000032:analysis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D000954:Antigens, Surface; D016207:Cytokines; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D005419:Flavonoids; D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; D007328:Insulin; D008070:Lipopolysaccharides; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051816:Tristetraprolin; D042461:Vascular Endothelial Growth Factor A