J Korean Med Sci.  2001 Aug;16(4):397-406. 10.3346/jkms.2001.16.4.397.

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

Affiliations
  • 1Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital. jrl@plaza.snu.ac.kr
  • 2Division of Cardiothoracic Surgery, Seoul Adventist Hospital.
  • 3Department of Pathology, Seoul National University Hospital, Seoul, Korea.

Abstract

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.

Keyword

NF-kappa B; Cytokines; Heart Transplantation; Coronary Arteriosclerosis; Graft Rejection

MeSH Terms

Animal
Chronic Disease
Coronary Arteriosclerosis/etiology/*metabolism
Cytokines/*biosynthesis
*Graft Rejection
*Heart Transplantation
Histocompatibility Antigens Class I/analysis
Intercellular Adhesion Molecule-1/biosynthesis
Interferon Type II/biosynthesis
Mice
NF-kappa B/*biosynthesis
Transplantation, Homologous
Tumor Necrosis Factor/biosynthesis
Vascular Cell Adhesion Molecule-1/biosynthesis
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