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Integrated Proteome and Cytokine Profiles Reveal Ceruloplasmin Eliciting Liver Allograft Tolerance via Antioxidant Cascades
Acute rejection (AR) and spontaneous tolerance may occur after allograft orthotopic liver transplants (OLT) performed in certain combinations of donor and recipient rat strains, yet the underlying molecular cascades involved in these conditions remain poorly understood. Comprehensive analysis with p...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168655/ https://www.ncbi.nlm.nih.gov/pubmed/30319655 http://dx.doi.org/10.3389/fimmu.2018.02216 |
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author | Wang, Pei-Wen Wu, Tung-Ho Pan, Tai-Long Chen, Mu-Hong Goto, Shigeru Chen, Chao-Long |
author_facet | Wang, Pei-Wen Wu, Tung-Ho Pan, Tai-Long Chen, Mu-Hong Goto, Shigeru Chen, Chao-Long |
author_sort | Wang, Pei-Wen |
collection | PubMed |
description | Acute rejection (AR) and spontaneous tolerance may occur after allograft orthotopic liver transplants (OLT) performed in certain combinations of donor and recipient rat strains, yet the underlying molecular cascades involved in these conditions remain poorly understood. Comprehensive analysis with proteomic tools revealed that ceruloplasmin was highly expressed during the tolerant period on day 63 post-OLT (POD 63) compared to the rejected samples on POD 14. Meanwhile, cytokine expression profiles implied that the inflammation was significantly stimulated in the AR subjects. Again, protein carbonylation was dramatically upregulated in the rejected subject within the tolerant group. Knockdown of ceruloplasmin would elicit more severe ROS damage, leading to cell death in the presence of H(2)O(2), which induced Nrf2 cascade and the recovery of ceruloplasmin to mediate spontaneous tolerance. In summary, ceruloplasmin may contribute to amending the oxidative stress that eventually causes cell apoptosis and to maintaining the survival of hepatocytes in a drug-free tolerance OLT model. |
format | Online Article Text |
id | pubmed-6168655 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61686552018-10-12 Integrated Proteome and Cytokine Profiles Reveal Ceruloplasmin Eliciting Liver Allograft Tolerance via Antioxidant Cascades Wang, Pei-Wen Wu, Tung-Ho Pan, Tai-Long Chen, Mu-Hong Goto, Shigeru Chen, Chao-Long Front Immunol Immunology Acute rejection (AR) and spontaneous tolerance may occur after allograft orthotopic liver transplants (OLT) performed in certain combinations of donor and recipient rat strains, yet the underlying molecular cascades involved in these conditions remain poorly understood. Comprehensive analysis with proteomic tools revealed that ceruloplasmin was highly expressed during the tolerant period on day 63 post-OLT (POD 63) compared to the rejected samples on POD 14. Meanwhile, cytokine expression profiles implied that the inflammation was significantly stimulated in the AR subjects. Again, protein carbonylation was dramatically upregulated in the rejected subject within the tolerant group. Knockdown of ceruloplasmin would elicit more severe ROS damage, leading to cell death in the presence of H(2)O(2), which induced Nrf2 cascade and the recovery of ceruloplasmin to mediate spontaneous tolerance. In summary, ceruloplasmin may contribute to amending the oxidative stress that eventually causes cell apoptosis and to maintaining the survival of hepatocytes in a drug-free tolerance OLT model. Frontiers Media S.A. 2018-09-26 /pmc/articles/PMC6168655/ /pubmed/30319655 http://dx.doi.org/10.3389/fimmu.2018.02216 Text en Copyright © 2018 Wang, Wu, Pan, Chen, Goto and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Wang, Pei-Wen Wu, Tung-Ho Pan, Tai-Long Chen, Mu-Hong Goto, Shigeru Chen, Chao-Long Integrated Proteome and Cytokine Profiles Reveal Ceruloplasmin Eliciting Liver Allograft Tolerance via Antioxidant Cascades |
title | Integrated Proteome and Cytokine Profiles Reveal Ceruloplasmin Eliciting Liver Allograft Tolerance via Antioxidant Cascades |
title_full | Integrated Proteome and Cytokine Profiles Reveal Ceruloplasmin Eliciting Liver Allograft Tolerance via Antioxidant Cascades |
title_fullStr | Integrated Proteome and Cytokine Profiles Reveal Ceruloplasmin Eliciting Liver Allograft Tolerance via Antioxidant Cascades |
title_full_unstemmed | Integrated Proteome and Cytokine Profiles Reveal Ceruloplasmin Eliciting Liver Allograft Tolerance via Antioxidant Cascades |
title_short | Integrated Proteome and Cytokine Profiles Reveal Ceruloplasmin Eliciting Liver Allograft Tolerance via Antioxidant Cascades |
title_sort | integrated proteome and cytokine profiles reveal ceruloplasmin eliciting liver allograft tolerance via antioxidant cascades |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168655/ https://www.ncbi.nlm.nih.gov/pubmed/30319655 http://dx.doi.org/10.3389/fimmu.2018.02216 |
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