Effect of epidermal growth factor and cyclosporin A on interleukin-8 gene expression in human aortic smooth muscle cells

Abstract

It was reported that accelerated allograft atherosclerosis is associated with usage of cyclosporin A (CsA). Although the immunosuppressive actions of CsA are extensively studied, the mechanisms of this adverse effect remains to be elucidated. Thus studied was whether CsA affects the expression of interleukin (IL)-8 in the primary culture of human aortic smooth muscle cells (HASMC) since IL-8 recently has been shown to be a mitogen and a chemoattractant for vascular smooth muscle cells (VSMC). Also studied was the effect of epidermal growth factor (EGF) on IL-8 expression because of its potent action of VSMC proliferation in the atherosclerotic lesion. Treatment of HASMC with CsA alone resulted in a significant increase in the IL-8 mRNA level. EGF also increased the mRNA level. CsA together with EGF further increased the IL-8 mRNA level. These results suggested that the CsA-dependent increase in IL-8 in VSMC could be one of the mechanisms for its induced accelerated allograft atherosclerosis.