Expression of NF-kappaB 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-kappaB/I-kappaB and cytokines (TNF-alpha, INF-gamma) were examined in these specimens. The expressions of TNF-alpha and INF-gamma were observed on day 1, peaking on day 5 and 7, respectively. Activated NF-kappaB (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-B 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-kappaB 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-kappaB/I-kappaB and cytokines (TNF-alpha, INF-gamma) 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.
Lee
J R
JR
Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Chongro-gu, Seoul, Korea. jrl@plaza.snu.ac.kr
Seok
C J
CJ
Kim
J S
JS
Chang
J M
JM
Seo
J W
JW
D000818:Animals; D002908:Chronic Disease; D003324:Coronary Artery Disease / Q000209:etiology / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis*; D006084:Graft Rejection; D016027:Heart Transplantation; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma