Heme oxygenase‐1 mediates the anti‐inflammatory effect of Curcumin within LPS‐stimulated human monocytes

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Abstract
Curcumin, a polyphenolic compound derived from plant, regulates heme oxygenase (HO‐1) expression within certain cell types; however, the Curcumin‐mediated signal transduction in the regulation of HO‐1 expression within human monocytes/macrophages is unclear. Herein, we show that Curcumin dose dependently induced HO‐1 expression and HO‐1 activity through the activation of PKCα, PKCδ/ERK1/2, p38α, and PI3‐kinase. In addition, H2O2 release is essential for Curcumin‐mediated ERK1/2 and p38 phosphorylation and HO‐1 expression. Further, Curcumin inhibited LPS‐induced IL‐1 and IL‐6 secretion and blockage of HO‐1 expression/activity by HO‐1 siRNA or HO‐1 inhibitor, SnPP reversed the inhibitory effects of Curcumin on cytokines secretion. HO‐1 over‐expression produced the same inhibitory effects of Curcumin on IL‐1 secretion. Collectively, our results suggest that Curcumin inhibits cytokines secretion within LPS‐stimulated monocytes through a mechanism that involves the action of HO‐1. J. Cell. Physiol. 215: 603–612, 2008.