Heme oxygenase-1 mediates the anti-inflammatory effect of curcumin within LPS-stimulated human monocytes

Curcumin, a polyphenolic compound derived from plant, regulates heme oxygenase (HO-I) expression within certain cell types; however, the Curcumin-mediated signal transduction in the regulation of HO-I expression within human monocytes/macrophages is unclear. Herein, we show that Curcumin dose dependently induced HO-I expression and HO-I activity through the activation of PKC alpha, PKC delta/ERK1/2, p38 alpha, and P13-kinase. In addition, H2O2 release is essential for Curcumin-mediated ERK1/2 and p38 phosphorylation and HO-I expression. Further, Curcumin inhibited LPS-induced IL-I and IL-6 secretion and blockage of HO-I expression/activity by HO-I siRNA or HO-I inhibitor, SnPP reversed the inhibitory effects of Curcumin on cytokines secretion. HO-I over-expression produced the same inhibitory effects of Curcumin on IL-I secretion. Collectively, our results suggest that Curcumin inhibits cytokines secretion within LPS-stimulated monocytes through a mechanism that involves the action of HO-I.