title: Cyclic AMP prolongs graft survival by suppressing apoptosis and inflammatory gene expression in acute cardiac allograft rejection.
abstract: This study was designed to investigate the effects of cAMP on immune regulation and apoptosis during acute rat cardiac allograft rejection. We found that the production of immune markers such as inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), iNOS expression, and nitric oxide (NO) production, was significantly increased in the blood and transplanted hearts of allograft recipients, but not of isograft controls. These increases were effectively suppressed by the administration of the membrane permeable cAMP analog dibutyryl cAMP (db-cAMP). Administration of db-cAMP reduced allograft-induced elevation of several biochemical markers, such as adhesion molecule expression, iron-nitrosyl complex formation, caspase-3 activation, and apoptotic DNA fragmentation in an animal model. Furthermore, treatment of allograft recipients with db-cAMP prolonged median graft survival to 11 days compared with a median graft survival time of 8 days in saline-treated allograft recipients. These results suggest that db-cAMP exerts a beneficial effect on murine cardiac allograft survival by modulating allogeneic immune response and cytotoxicity.
authors.affiliation: Vascular System Research Center, School of Medicine, Kangwon National University, Chuncheon, Korea.
authors.forename: Jie-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Gibong
authors.initials: G
authors.lastname: Chae
authors.forename: Bong-Ki
authors.initials: BK
authors.lastname: Lee
authors.forename: Kwon-Soo
authors.initials: KS
authors.lastname: Ha
authors.forename: Young-Geun
authors.initials: YG
authors.lastname: Kwon
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use*; D004578:Electron Spin Resonance Spectroscopy; D006084:Graft Rejection / Q000188:drug therapy*; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000009:adverse effects*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000242:Cyclic AMP; D052247:Nitric Oxide Synthase Type II; D053148:Caspase 3