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Park 7: A Novel Therapeutic Target for Macrophages in Sepsis-Induced Immunosuppression

Sepsis remains a serious and life-threatening condition with high morbidity and mortality due to uncontrolled inflammation together with immunosuppression with few therapeutic options. Macrophages are recognized to play essential roles throughout all phases of sepsis and affect both immune homeostas...

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Autores principales: Cheng, Yanwei, Marion, Tony N., Cao, Xue, Wang, Wanting, Cao, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277877/
https://www.ncbi.nlm.nih.gov/pubmed/30542343
http://dx.doi.org/10.3389/fimmu.2018.02632
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author Cheng, Yanwei
Marion, Tony N.
Cao, Xue
Wang, Wanting
Cao, Yu
author_facet Cheng, Yanwei
Marion, Tony N.
Cao, Xue
Wang, Wanting
Cao, Yu
author_sort Cheng, Yanwei
collection PubMed
description Sepsis remains a serious and life-threatening condition with high morbidity and mortality due to uncontrolled inflammation together with immunosuppression with few therapeutic options. Macrophages are recognized to play essential roles throughout all phases of sepsis and affect both immune homeostasis and inflammatory processes, and macrophage dysfunction is considered to be one of the major causes for sepsis-induced immunosuppression. Currently, Parkinson disease protein 7 (Park 7) is known to play an important role in regulating the production of reactive oxygen species (ROS) through interaction with p47(phox), a subunit of NADPH oxidase. ROS are key mediators in initiating toll-like receptor (TLR) signaling pathways to activate macrophages. Emerging evidence has strongly implicated Park 7 as an antagonist for sepsis-induced immunosuppression, which suggests that Park 7 may be a novel therapeutic target for reversing immunosuppression compromised by sepsis. Here, we review the main characteristics of sepsis-induced immunosuppression caused by macrophages and provide a detailed mechanism for how Park 7 antagonizes sepsis-induced immunosuppression initiated by the macrophage inflammatory response. Finally, we further discuss the most promising approach to develop innovative drugs that target Park 7 in patients whose initial presentation is at the late stage of sepsis.
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spelling pubmed-62778772018-12-12 Park 7: A Novel Therapeutic Target for Macrophages in Sepsis-Induced Immunosuppression Cheng, Yanwei Marion, Tony N. Cao, Xue Wang, Wanting Cao, Yu Front Immunol Immunology Sepsis remains a serious and life-threatening condition with high morbidity and mortality due to uncontrolled inflammation together with immunosuppression with few therapeutic options. Macrophages are recognized to play essential roles throughout all phases of sepsis and affect both immune homeostasis and inflammatory processes, and macrophage dysfunction is considered to be one of the major causes for sepsis-induced immunosuppression. Currently, Parkinson disease protein 7 (Park 7) is known to play an important role in regulating the production of reactive oxygen species (ROS) through interaction with p47(phox), a subunit of NADPH oxidase. ROS are key mediators in initiating toll-like receptor (TLR) signaling pathways to activate macrophages. Emerging evidence has strongly implicated Park 7 as an antagonist for sepsis-induced immunosuppression, which suggests that Park 7 may be a novel therapeutic target for reversing immunosuppression compromised by sepsis. Here, we review the main characteristics of sepsis-induced immunosuppression caused by macrophages and provide a detailed mechanism for how Park 7 antagonizes sepsis-induced immunosuppression initiated by the macrophage inflammatory response. Finally, we further discuss the most promising approach to develop innovative drugs that target Park 7 in patients whose initial presentation is at the late stage of sepsis. Frontiers Media S.A. 2018-11-13 /pmc/articles/PMC6277877/ /pubmed/30542343 http://dx.doi.org/10.3389/fimmu.2018.02632 Text en Copyright © 2018 Cheng, Marion, Cao, Wang and Cao. 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
Cheng, Yanwei
Marion, Tony N.
Cao, Xue
Wang, Wanting
Cao, Yu
Park 7: A Novel Therapeutic Target for Macrophages in Sepsis-Induced Immunosuppression
title Park 7: A Novel Therapeutic Target for Macrophages in Sepsis-Induced Immunosuppression
title_full Park 7: A Novel Therapeutic Target for Macrophages in Sepsis-Induced Immunosuppression
title_fullStr Park 7: A Novel Therapeutic Target for Macrophages in Sepsis-Induced Immunosuppression
title_full_unstemmed Park 7: A Novel Therapeutic Target for Macrophages in Sepsis-Induced Immunosuppression
title_short Park 7: A Novel Therapeutic Target for Macrophages in Sepsis-Induced Immunosuppression
title_sort park 7: a novel therapeutic target for macrophages in sepsis-induced immunosuppression
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277877/
https://www.ncbi.nlm.nih.gov/pubmed/30542343
http://dx.doi.org/10.3389/fimmu.2018.02632
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