Chronic Graft Dysfunction and Improvement by Cytokine Response Modifier a Protein Transfection

Abstract

Objectives: Cytokine response modifier A protein is a caspase inhibitor that inhibits caspase activity and protects cells from apoptosis. Chronic cyclosporine nephropathy is a significant cause of chronic graft dysfunction. We explored cytokine response modifier A protein-alleviated chronic cyclosporine nephropathy for ways of improving chronic graft dysfunction.

Materials and Methods: Cytokine response modifier A protein-transferring HK-2 cells were cultured with different concentrations of cyclosporine. Cytokine response modifier A protein mRNA and proteins were detected by real-time polymerase chain reaction and Western blot, cell viability was detected by (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), and apoptosis was detected by flow cytometry.

Results: Cyclosporine caused a concentration-dependent and time-dependent loss of cell viability in HK-2 cells. Cytokine response modifier A protein mRNA was expressed at 48 and 72 hours (P < .05), while protein was detected at 72 hours. Cell viability in the cytokine response modifier A protein-transfected group was significantly greater than that of the control group when treated with 1 µg/mL, 10 µg/mL, or 20 µg/mL cyclosporine at 24 or 48 hours (P < .05). The apoptosis in cytokine response modifier A protein-transfected cells was significantly lower than that of controls (P < .05).

Conclusions: Cytokine response modifier A protein protects renal cells from cyclosporine injury by inhibiting activated caspases. Cytokine response modifier A protein transfection may improve chronic cyclosporine nephropathy and provide for improving chronic graft dysfunction.