title: Transcriptional activation of nuclear-related factor 2 by FK506 in Jurkat T cells.
abstract: BACKGROUND
  We 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 24 hours and then decreased after 48 hours.
  
  
  RESULTS
  We 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 24 hours, and then decreased after 48 hours.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Surgery, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Y W
authors.initials: YW
authors.lastname: Chung
authors.affiliation: Department of Surgery, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Y M
authors.initials: YM
authors.lastname: Jeong
authors.affiliation: Department of Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: M W
authors.initials: MW
authors.lastname: Chung
authors.affiliation: Department of Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: S K
authors.initials: SK
authors.lastname: Choi
authors.affiliation: Department of Surgery, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: S J N
authors.initials: SJ
authors.lastname: Choi
authors.affiliation: Department of Surgery, Chonnam National University Medical School, Gwangju, Korea. Electronic address: sycpvts@chonnam.ac.kr.
authors.forename: S Y
authors.initials: SY
authors.lastname: Chung
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019169:Jurkat Cells; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D051547:Heme Oxygenase-1; D016559:Tacrolimus