FK506: an immunosuppressive agent preserving HIF-1 activity

During transplantation, donor organs or cells are subjected to hypoxia. Hypoxia-inducible factor-1 (HIF-1) is essential for cellular adaptation to hypoxia. Immunosuppressive agents should be used for preventing graft rejection, but of these, rapamycin and cyclosporine A have been reported to inhibit HIF-1. We examined whether or not another important immunosuppressant, FK506, inhibits HIF-1. In contrast to cyclosporine A, FK506 neither inhibits HIF-1alpha expression in 8 different cell lines, nor represses the transcriptional activity of HIF-1. Compared with cyclosporine A, FK506 significantly reduced the apoptotic cell death by hypoxia. FK506 could preserve HIF-1 activity in donor organs subjected to hypoxia.