Expression of NF-kappa B and cytokines in chronic rejection of transplanted murine heart

The heart transplantation-associated accelerated graft arteriosclerosis (AG AS) is one of the major causes of cardiac allograft failure. We investigate d the early time-course of expression patterns of cytokines, transcription factor, and its inhibitor in the intraabdominally transplanted mice hearts that differed only in the D locus of class 1 histocompatibility antigen. Th e allograft hearts were harvested at 1-3, 5, 7, 14, 28, and 42 days after t he transplantation, and the expressions of NF-kappaB/I-kappaB and cytokines (TNF-alpha, INF-gamma) were examined in these specimens. The expressions o f TNF-alpha and INF-gamma were observed on day 1, peaking on day 5 and 7, r espectively. Activated NF-kappaB (p65) expression was present on the cytopl asm and perinuclear area in the endothelial cells of coronary arteries on d ay 1. The peak of translocation of NF-kappaB from cytoplasm to nucleus appe ared on day 5 in the endothelial cells, myocytes, and leukocytes within the vessels, and remained elevated until day 42. The I-kappaB expression gradu ally increased from day 1 until day 5, but a remarkable decrease was detect ed on day 7. Our data suggest that the increased expressions of NF-kappaB/I -kappaB and cytokines (TNF-a, INF-gamma) play an important role in inducing immune responses in the donor allograft heart and hence the blockage of th e expressions might be mandatory to avoid a potential graft failure.