Effect Of Homocysteine On Expression Of Interleukin-8 MRNA And Protein In THP-1 Macrophages

BackgroundHomocysteine is a sulfur-containing amino acid formed during the metabolism of methionine. Hyperhomocysteinemia was found in 20~30% of patients with premature atherosclerosis involving carotid, coronary and peripheral artery. Elevated plasma levels of homocysteine (Hcy) is an established risk factor for atherosclerotic disease. Recent studies demonstrate that Hcy can enhance endothelial dysfunction and promote the proliferation of vascular smooth muscle cells. However, the underlying molecular mechanisms are not fully elucidated. And it is agreed that atherosclerosis is an inflammatory process in which cytokines played important roles. Interleukin-8(IL-8) is a multifunctional pro inflammatory cytokine that is expressed in macrophage-rich areas of human coronary atheromas and the pathogenicity of this chemokine is mostly attributed toits chemotactic activity toward neutrophils , T-cells, monocytes, smooth muscle, and endothelial cells, as well as to its mitotic and angiogenic properties. The effect of Hcy on the expression of IL-8 in atherogenesis and the underling mechanisms are still uncertain untill now. To have a better understand the role of elevated homocysteine levels in the pathogenesis of atherosclerosis, we examined the effect of homocysteine on the expression and secretion of IL-8 in THP-1 macrophages at concentrations similar to those observed in clinical studies. We found that homocysteine increased the expression of IL-8mRNA and secretion of IL-8 protein. Object:To determine whether Hey contribute to the pathogenesis of atherosclerosis by increasing the expression of IL-8 mRNA and the production of IL-8 protein by means of investigating the effect of Hey on human THP-1 macrophages. Methods:Human THP-1 macrophages were stimulated with Hcy. ELISA was performed to measure the expression of IL-8 protein. Semiquantitative RT-PCR was used to detect the IL-8 mRNA expression. Results:Hcy concentration-dependently increased the production of IL-8 protein in human THP-1 macrophages. Compared with control, Hcy of0. 05mmol/L, 0.1mmol/L and 0. 2mmol/L concentration increased IL-8 production to 1.28 fold, 1.32 fold and 1.55 fold respectively (P<0. 01 ) .And IL-8 production were elevated significantly after 3h when treated with 0. Immol/L Hcy. In addition, Hcy also increased IL-8 mRNA expression in a concentration-and time-dependent manner. Conclusion:Hey may contribute to atherogenesis by induction of IL-8 expression and secretion in THP-1 macrophage.