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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chronic Disease
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / metabolism*
  • Cytokines / biosynthesis*
  • Graft Rejection*
  • Heart Transplantation*
  • Histocompatibility Antigens Class I / analysis
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Interferon-gamma / biosynthesis
  • Mice
  • NF-kappa B / biosynthesis*
  • Transplantation, Homologous
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Vascular Cell Adhesion Molecule-1 / biosynthesis

Substances

  • Cytokines
  • Histocompatibility Antigens Class I
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma