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Effects of Monocyte Chemotactic Protein-1 and Nuclear Factor of Kappa B Pathway in Rejection of Cardiac Allograft in Rat.

AbstractBACKGROUND:
Graft rejection is a key obstacle to successful heart transplantation. We sought to investigate the expression and role of monocyte chemotactic protein-1 (MCP-1) in rejection of cardiac allografts, as well as the role of the nuclear factor of kappa B (NF-κB) pathway.
METHODS:
Heterotopic cervical heart transplantation was performed using a modified cuff-technique. Recipient rats (n = 12) underwent acute rejection (AR) without any treatment (AR group). The remaining rats (3 groups; n = 12/group) were treated with Cyclosporine A (CsA; CsA group), immunologic tolerance (IT; IT group), and pyrrolidine dithiocarbamate (PDTC; NF-κB inhibitor; PDTC group). We studied the inflammatory infiltration and myocardial fibrosis of cardiac allografts with hematoxylin-eosin (HE) and Masson staining, and detected the expression of MCP-1 by immunohistochemistry and Western blotting. Cardiac allograft vasculopathy (CAV) also was evaluated using van Gieson staining.
RESULTS:
The survival time of the PDTC group (142.37 ± 24.28 days) was significantly longer than that of the AR group (6.54 ± 2.47 days; P = .00073) and the CsA group (93.51 ± 20.17 days; P = .0052). Myocardial fibrosis and CAV in the PDTC group were significantly attenuated compared with the CsA group (P < .01). The expression of MCP-1 in the IT group was markedly lower than in the other 3 groups (P < .05). The expression of MCP-1 in the PDTC group was also significantly lower than the CsA group (1.15 ± 0.27 vs 1.58 ± 0.17; P = .016).
CONCLUSION:
These findings suggest that the expression level of MCP-1 could be monitored to reflect the severity of cardiac allograft rejection. PDTC can significantly prevent the rejection of cardiac allografts by inhibiting MCP-1 expression via the suppression of the NF-κB pathway.
AuthorsX Bai, Z Qi, G Song, X Zhao, H Zhao, X Meng, C Liu, W Bing, Y Bi
JournalTransplantation proceedings (Transplant Proc) 2015 Jul-Aug Vol. 47 Issue 6 Pg. 2010-6 ISSN: 1873-2623 [Electronic] United States
PMID26293090 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Chemokine CCL2
  • NF-kappa B
Topics
  • Allografts
  • Animals
  • Blotting, Western
  • Chemokine CCL2 (metabolism)
  • Disease Models, Animal
  • Graft Rejection (immunology, metabolism)
  • Heart Transplantation
  • NF-kappa B (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar

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