Cyclic AMP prolongs graft survival by suppressing apoptosis and inflammatory gene expression in acute cardiac allograft rejection.
10.3858/emm.2010.42.1.008
- Author:
Jie Young LEE
1
;
Jung Hwan KIM
;
Gibong CHAE
;
Bong Ki LEE
;
Kwon Soo HA
;
Young Geun KWON
;
Young Myeong KIM
Author Information
1. Vascular System Research Center, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea. ymkim@kangwon.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
cyclic AMP;
cytokines;
graft rejections;
heart transplantation;
inflammation;
nitric oxide
- MeSH:
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
- From:Experimental & Molecular Medicine
2010;42(1):69-79
- CountryRepublic of Korea
- Language:English
-
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.
