Epigallocatechin gallate–mediated protection against tumor necrosis factor-α–induced monocyte chemoattractant protein–1 expression is heme oxygenase–1 dependent

Abstract 

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.