Heme oxygenase-1-mediated reactive oxygen species reduction is involved in the inhibitory effect of curcumin on lipopolysaccharide-induced monocyte chemoattractant protein-1 production in RAW264.7 macrophages

Abstract

Monocyte chemoattractant protein 1 (MCP-1) is a CCchemokine which stimulates mononuclear leukocytes and is significant in the pathogenesis of inflammatory disease. Curcumin, extracted from Curcumae longae, has been shown to possess anti-inflammatory activity, in inflammation associated with the induction of MCP-1 expression. However, the underlying mechanisms involved in the effect of curcumin on MCP-1 expression remain unclear. In the current study, we investigated the effect of curcumin on the production of MCP-1 induced by lipopolysaccharide (LPS) in macrophages and the possible mechanisms involved. The results revealed that curcumin decreased MCP-1 production in a concentration-dependent manner and reduced the generation of reactive oxygen species (ROS) induced by LPS in RAW264.7 macrophages. Additionally, zinc protoporphyrin, a heme oxygenase-1 (HO-1) inhibitor, blocked the inhibitory effect of curcumin on the LPS-induced MCP-1 expression. The exposure of cells to curcumin was found to enhance HO-1 expression. Furthermore, additional experiments indicated that the inhibitory effect of curcumin on LPS-induced MCP-1 expression was significantly attenuated in the presence of N-acetylcysteine (an effective ROS scavenger). The results presented in our study suggest that curcumin enhances the expression of HO-1 to reduce the LPS-induced production of ROS, which leads to the inhibition of MCP-1 expression in RAW264.7 macrophages.