Epigallocatechin gallate-mediated protection against tumor necrosis factor-α-induced monocyte chemoattractant protein-1 expression is heme oxygenase-1 dependent.
Flavonoids have been suggested to protect against atherosclerosis via their antioxidant and anti-inflammatory properties. Heme oxygenase-1 (HO-1) is an enzyme that plays an important role in the vascular system, and its induction may provide a protective role against atherosclerosis. We hypothesize that flavonoids can down-regulate endothelial inflammatory parameters by modulating HO-1-regulated cell signaling. We focused on the role of HO-1 and its major metabolic product, bilirubin, on mechanisms of tumor necrosis factor-α-induced endothelial cell activation and protection by the catechin epigallocatechin gallate (EGCG). Pretreatment with EGCG inhibited the secretion of monocyte chemoattractant protein-1 and the activation of activator protein-1 in porcine aortic endothelial cells stimulated with tumor necrosis factor-α. Moreover, EGCG up-regulated the expression of HO-1 and further induced the secretion of bilirubin. The observed anti-inflammatory effects of EGCG were mimicked by the HO-1 inducer cobalt protoporphyrin and abolished by HO-1 gene silencing. These data suggest that the protective properties of flavonoids, such as EGCG, against endothelial inflammation may be regulated in part though induction of HO-1 and subsequent activator protein-1 signaling.
Zheng
Yuanyuan
Y
Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY 40536-0200, USA.
Toborek
Michal
M
Hennig
Bernhard
B
D000818:Animals; D001663:Bilirubin / Q000378:metabolism / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000235:genetics*; D019610:Cytoprotection / Q000187:drug effects* / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D013552:Swine; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D018932:Chemokine CCL2; D020319:Oligodeoxyribonucleotides, Antisense; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin; C045651:epigallocatechin gallate; D051547:Heme Oxygenase-1; D001663:Bilirubin