Expression of NF-κB and Cytokines in Chronic Rejection of Transplanted Murine Heart

The heart transplantation-associated accelerated graft arteriosclerosis (AGAS) is one of the major causes of cardiac allograft failure. We investigated the early time-course of expresssion patterns of cytokines, transcription factor, and its inhibitor in the intraabdominally transplanted mice hearts that differed only in the D locus of class I histocompatibility antigen. The allograft hearts were harvested at 1-3, 5, 7, 14, 28, and 42 days after the transplantation, and the expressions of NF-κB/I-κB and cytokines (TNF-α , INF-γ) were examined in these specimens. The expressions of TNF-α and INF-γ were observed on day 1, peaking on day 5 and 7, respectively. Activated NF-αB (p65) expression was present on the cytoplasm and perinuclear area in the endothelial cells of coronary arteries on day 1. The peak of translocation of NF-αB from cytoplasm to nucleus appeared on day 5 in the endothelial cells, myocytes, and leukocytes within the vessels, and remained elevated until day 42. The I-αB expression gradually increased from day 1 until day 5, but a remarkable decrease was detected on day 7. Our data suggest that the increased expressions of NF-αB/I-αB and cytokines (TNF-α, INF-γ) play an important role in inducing immune responses in the donor allograft heart and hence the blockage of the expressions might be mandatory to avoid a potential graft failure.