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Am J Physiol Heart Circ Physiol 280: H2840-H2847, 2001;
0363-6135/01 $5.00
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Vol. 280, Issue 6, H2840-H2847, June 2001

Homocysteine induces monocyte chemoattractant protein-1 expression by activating NF-kappa B in THP-1 macrophages

Guoping Wang, Yaw L. Siow, and Karmin O

Department of Pharmacology and Institute of Cardiovascular Science and Medicine, Faculty of Medicine, University of Hong Kong, Hong Kong, China

Homocysteinemia is an independent risk factor for cardiovascular disorders. The recruitment of monocytes is an important event in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that stimulates monocyte migration into the intima of arterial walls. The objective of the present study was to investigate the effect of homocysteine on MCP-1 expression in macrophages and the underlying mechanism of such effect. Human monocytic cell (THP-1)-derived macrophages were incubated with homocysteine. By nuclease protection assay and ELISA, homocysteine (0.05-0.2 mM) was shown to significantly enhance the expression of MCP-1 mRNA (up to 2.6-fold) and protein (up to 4.8-fold) in these cells. Homocysteine-induced MCP-1 expression resulted in increased monocyte chemotaxis. The increase in MCP-1 expression was associated with activation of nuclear factor (NF)-kappa B due to increased phosphorylation of the inhibitory protein (Ikappa B-alpha ) as well as reduced expression of Ikappa B-alpha mRNA in homocysteine-treated cells. In conclusion, our results demonstrate that homocysteine, at pathological concentration, stimulates MCP-1 expression in THP-1 macrophages via NF-kappa B activation.

chemotaxis; inhibitory protein; Ikappa B-alpha ; atherosclerosis; nuclear factor-kappa B


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