10th Japan-Korea transplantation forumExperimental transplantationTranscriptional Activation of Nuclear-Related Factor 2 by FK506 in Jurkat T Cells

•FK506 treatment increased the generation of ROS and reactive nitrogen species in Jurkat cells in a dose-dependent manner.•We found that a marked dissociation of Nrf 2 from Keap 1 and subsequently Nrf2 nuclear translocation occurred in Jurkat cells treated with FK506 for 48 hours.•We noted that the FK506 treatment increased expression of HO-1 in Jurkat cells in a dose-dependent manner.•We confirmed that FK506 induces Nrf 2-driven transcriptional activation of antioxidant response element by activating HO-1 and free radicals such as ROS and NO.

BackgroundWe investigated the effect of FK506 in transcriptional activation of nuclear factor (erythroid-derived 2)-like2 (Nrf2) in human Jurkat T cells. Methods. FK506 treatment increased the generation of reactive oxygen species and reactive nitrogen species in Jurkat cells in a dose-dependent manner. Generation of nitric oxide was also increased after treatment with FK506 in Jurkat cells. Peak levels of endothelial nitricoxide synthase expression occurred at 24hours and then decreased after 48 hours.ResultsWe found that a marked dissociation of Nrf 2 from Kelch-like ECH-associated protein-1 and subsequently Nrf 2 nuclear translocation occurred in Jurkat cells treated with FK506 during 48 hours. Immunohistochemistry and Western blot analysis data revealed that the FK506 treatment increased expression of heme oxygenase-1 (HO-1) in Jurkat cells in a dose-dependent manner. HO-1 expression was induced after 6 hours of treatment of FK506 to Jurkat cells, peaked at 24hours, and then decreased after 48 hours.ConclusionsThese results suggest that FK506 induces Nrf 2-driven transcriptional activation of the antioxidant response element by activating HO-1 and free radicals such as reactive oxygen species and nitric oxide.