Exp Mol Med.
2010 Jan;42(1):69-79. 10.3858/emm.2010.42.1.008.
Cyclic AMP prolongs graft survival by suppressing apoptosis and inflammatory gene expression in acute cardiac allograft rejection
- Affiliations
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- 1Vascular System Research Center, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea. ymkim@kangwon.ac.kr
- 2Department of Surgery, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
- 3Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
- 4Cardiovascular Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
- 5Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-752, Korea.
- KMID: 946671
- DOI: http://doi.org/10.3858/emm.2010.42.1.008
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.
Keyword
MeSH Terms
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Animals
Apoptosis/drug effects
Caspase 3/metabolism
Cyclic AMP/analogs & derivatives/*pharmacology/*therapeutic use
Electron Spin Resonance Spectroscopy
Graft Rejection/*drug therapy
Graft Survival/*drug effects
Heart Transplantation/*adverse effects
Interleukin-1beta/metabolism
Interleukin-6/metabolism
Male
Nitric Oxide/metabolism
Nitric Oxide Synthase Type II/genetics
Rats
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor-alpha/metabolism
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