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

Homocysteinemia is an independent risk factor for cardiovascular disorders. The recruitment of monocytes is an important event in atherogenesis. Monoc yte 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 expre ssion in macrophages and the underlying mechanism of such effect. Human mon ocytic cell (THP-1)-derived macrophages were incubated with homocysteine. B y 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 expres sion resulted in increased monocyte chemotaxis. The increase in MCP-1 expre ssion was associated with activation of nuclear factor (NF)-kappaB due to i ncreased phosphorylation of the inhibitory protein (I kappaB-alpha) as well as reduced expression of I kappaB-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-kap paB activation.