Cargando…

Anti-4-1BB monoclonal antibodies attenuate concanavalin A-induced immune-mediated liver injury in mice

Effective therapies for the treatment of immune-mediated liver disease are currently lacking. As a member of the tumor necrosis factor receptor superfamily, 4-1BB has a key role in T-cell activation and has been implicated in the development of autoimmune disorders. The purpose of the present study...

Descripción completa

Detalles Bibliográficos
Autores principales: Xia, Guangtao, Wu, Sensen, Zhang, Yuanchao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998111/
https://www.ncbi.nlm.nih.gov/pubmed/27588047
http://dx.doi.org/10.3892/etm.2016.3503
_version_ 1782449881660522496
author Xia, Guangtao
Wu, Sensen
Zhang, Yuanchao
author_facet Xia, Guangtao
Wu, Sensen
Zhang, Yuanchao
author_sort Xia, Guangtao
collection PubMed
description Effective therapies for the treatment of immune-mediated liver disease are currently lacking. As a member of the tumor necrosis factor receptor superfamily, 4-1BB has a key role in T-cell activation and has been implicated in the development of autoimmune disorders. The purpose of the present study was to evaluate the potential therapeutic or preventive function of an anti-4-1BB monoclonal antibody (mAb) in a mouse model of concanavalin (Con) A-induced immune-mediated liver injury. A mouse model of immune-mediated liver injury was established by tail vein injection of Con A (20 mg/kg). 4-1BB mAb (100 µg), with or without methylprednisolone (MEP; 3 mg/kg), was intraperitoneally injected into the tail vein 2 h prior to or 2 h following Con A injection. Con A induced marked hepatocyte necrosis, significantly reduced CD 4(+)/CD25(+) T-cell levels, and increased the serum levels of aspartate transaminase (AST) and alanine transaminase (ALT), in addition to the percentage of 4-1BB(+) T-cells, compared with the control (all P<0.05). The administration of 4-1BB mAb prior to or following Con A injection was able to attenuate Con A-induced liver tissue damage and significantly reduce serum AST and ALT levels (P<0.05). A combination of MEP and 4-1BB mAb further reduced serum AST and ALT levels, compared with either treatment alone. In addition, administration of 4-1BB mAb and MEP alone or in combination significantly increased CD4(+)/CD25(+) T-cell levels, compared with the control (P<0.05). These results suggested that 4-1BB mAb was able to attenuate liver injury and preserve liver function in a mouse model of Con A-induced immune-mediated liver injury by promoting the expansion of CD4(+)/CD25(+) T-cells. Furthermore, a combination of 4-1BB mAb with MEP was associated with greater beneficial effects than either treatment alone. The clinical significance of 4-1BB mAb in immune-mediated liver disease remains to be elucidated in future studies.
format Online
Article
Text
id pubmed-4998111
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-49981112016-09-01 Anti-4-1BB monoclonal antibodies attenuate concanavalin A-induced immune-mediated liver injury in mice Xia, Guangtao Wu, Sensen Zhang, Yuanchao Exp Ther Med Articles Effective therapies for the treatment of immune-mediated liver disease are currently lacking. As a member of the tumor necrosis factor receptor superfamily, 4-1BB has a key role in T-cell activation and has been implicated in the development of autoimmune disorders. The purpose of the present study was to evaluate the potential therapeutic or preventive function of an anti-4-1BB monoclonal antibody (mAb) in a mouse model of concanavalin (Con) A-induced immune-mediated liver injury. A mouse model of immune-mediated liver injury was established by tail vein injection of Con A (20 mg/kg). 4-1BB mAb (100 µg), with or without methylprednisolone (MEP; 3 mg/kg), was intraperitoneally injected into the tail vein 2 h prior to or 2 h following Con A injection. Con A induced marked hepatocyte necrosis, significantly reduced CD 4(+)/CD25(+) T-cell levels, and increased the serum levels of aspartate transaminase (AST) and alanine transaminase (ALT), in addition to the percentage of 4-1BB(+) T-cells, compared with the control (all P<0.05). The administration of 4-1BB mAb prior to or following Con A injection was able to attenuate Con A-induced liver tissue damage and significantly reduce serum AST and ALT levels (P<0.05). A combination of MEP and 4-1BB mAb further reduced serum AST and ALT levels, compared with either treatment alone. In addition, administration of 4-1BB mAb and MEP alone or in combination significantly increased CD4(+)/CD25(+) T-cell levels, compared with the control (P<0.05). These results suggested that 4-1BB mAb was able to attenuate liver injury and preserve liver function in a mouse model of Con A-induced immune-mediated liver injury by promoting the expansion of CD4(+)/CD25(+) T-cells. Furthermore, a combination of 4-1BB mAb with MEP was associated with greater beneficial effects than either treatment alone. The clinical significance of 4-1BB mAb in immune-mediated liver disease remains to be elucidated in future studies. D.A. Spandidos 2016-09 2016-06-24 /pmc/articles/PMC4998111/ /pubmed/27588047 http://dx.doi.org/10.3892/etm.2016.3503 Text en Copyright: © Xia et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Xia, Guangtao
Wu, Sensen
Zhang, Yuanchao
Anti-4-1BB monoclonal antibodies attenuate concanavalin A-induced immune-mediated liver injury in mice
title Anti-4-1BB monoclonal antibodies attenuate concanavalin A-induced immune-mediated liver injury in mice
title_full Anti-4-1BB monoclonal antibodies attenuate concanavalin A-induced immune-mediated liver injury in mice
title_fullStr Anti-4-1BB monoclonal antibodies attenuate concanavalin A-induced immune-mediated liver injury in mice
title_full_unstemmed Anti-4-1BB monoclonal antibodies attenuate concanavalin A-induced immune-mediated liver injury in mice
title_short Anti-4-1BB monoclonal antibodies attenuate concanavalin A-induced immune-mediated liver injury in mice
title_sort anti-4-1bb monoclonal antibodies attenuate concanavalin a-induced immune-mediated liver injury in mice
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998111/
https://www.ncbi.nlm.nih.gov/pubmed/27588047
http://dx.doi.org/10.3892/etm.2016.3503
work_keys_str_mv AT xiaguangtao anti41bbmonoclonalantibodiesattenuateconcanavalinainducedimmunemediatedliverinjuryinmice
AT wusensen anti41bbmonoclonalantibodiesattenuateconcanavalinainducedimmunemediatedliverinjuryinmice
AT zhangyuanchao anti41bbmonoclonalantibodiesattenuateconcanavalinainducedimmunemediatedliverinjuryinmice