Fig. 6.

FK506 reduces calcineurin activity in both the cytoplasm and nucleus. In the cytoplasm, FK506 reduces renal tubular cell death by inhibiting calcineurin expression. Inhibition of calcineurin decreases the levels of dephosphorylated NFAT2. Thus, FK506 reduces the neutrophil infiltration and production of pro-inflammatory cytokines induced by renal injury, as shown in this study. FK506 decreases calcineurin activity by inhibiting its calpain-catalyzed cleavage. Cleaved calcineurin is known to be cytotoxic by enhancing NFAT2 transcriptional activity following ischemia/reperfusion injury.