Stimulation of Endothelin mRNA and Secretion in Human Endothelial Cells by FK 506

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Abstract
FK 506 is a powerful new immunosuppressant that is more effective in preventing and treating allograft rejection than cyclosporine (CyA). This study was undertaken to examine the effect of FK 506 on stimulation of endothelin-1 (ET-1) mRNA and secretion of ET-1 in human endothelial cells (EC) compared with the effects of CyA. The dose of 0.1 microM of CyA used in clinical practice induced expression of ET-1 mRNA and increased secretion of ET-1 in EC. The same dose of FK 506 had the same effect. A clinical dose of 0.01 microM of FK 506 did not induce expression of ET-1 mRNA and did not increase the secretion of ET-1 in EC. These findings suggest that the lower incidence of complications seen with FK 506 is due in part to its use at a lower clinical dose compared with that of CyA.