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KMID : 0620920100420010069
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Experimental & Molecular Medicine
2010 Volume.42 No. 1 p.69 ~ p.79
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Cyclic AMP prolongs graft survival by suppressing apoptosis and inflammatory gene expression in acute cardiac allograft rejection
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Lee Jie-Young
Kim Jung-Hwan
Chae Gi-Bong
Lee Bong-Ki
Ha Kwon-Soo
Kwon Young-Geun
Kim Young-Myeong
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Abstract
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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-1β, IL-6, and TNF-α), 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.
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KEYWORD
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apoptosis, cyclic AMP, cytokines, graft rejections, heart transplantation, inflammation, nitric oxide
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