title: Nrf2 is crucial to graft survival in a rodent model of heart transplantation.
abstract: Currently, the sole treatment option for patients with heart failure is transplantation. The battle of prolonging graft survival and modulating innate and adaptive immune responses is still being waged in the clinic and in research labs. The transcription factor Nrf2 controls major cell survival pathways and is central to moderating inflammation and immune responses. In this study the effect of Nrf2 levels in host recipient C57BL/6 mice on Balb/c allogeneic graft survival was examined. Importantly, Nrf2(-/-) recipient mice could not support the graft for longer than 7.5 days on average, whereas activation of Nrf2 by sulforaphane in Nrf2(+/+) hosts prolonged graft survival to 13 days. Several immune cells in the spleen of recipient mice were unchanged; however, CD11b(+) macrophages were significantly increased in Nrf2(-/-) mice. In addition, IL-17 mRNA levels were elevated in grafts transplanted into Nrf2(-/-) mice. Although Nrf2 appears to play a crucial role in graft survival, the exact mechanism is yet to be fully understood.
authors.affiliation: Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Quan
authors.initials: Q
authors.lastname: Qiu
authors.forename: Huihui
authors.initials: H
authors.lastname: Wang
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Whitman
authors.forename: Deyu
authors.initials: D
authors.lastname: Fang
authors.forename: Fangru
authors.initials: F
authors.lastname: Lian
authors.forename: Donna D
authors.initials: DD
authors.lastname: Zhang
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D006084:Graft Rejection / Q000188:drug therapy; D006085:Graft Survival / Q000276:immunology*; D006333:Heart Failure / Q000628:therapy; D016027:Heart Transplantation; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D017879:Isothiocyanates; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013454:Sulfoxides; D013861:Thiocyanates / Q000627:therapeutic use; D014184:Transplantation, Homologous
chemical_list: D039481:CD11b Antigen; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D012333:RNA, Messenger; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane