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Interference with KCTD9 inhibits NK cell activation and ameliorates fulminant liver failure in mice

BACKGROUND: Potassium channel tetramerisation domain containing 9 (KCTD9), a member of KCTD family with a DNA-like pentapeptide repeat domain, was found to be increased particularly in NK cells of patients with HBV-induced acute-on-chronic liver failure (HBV-ACLF) and experimental viral fulminant he...

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Autores principales: Zhang, Xiaoping, Zhu, Lin, Zhou, Yaoyong, Shi, Aichao, Wang, Hongwu, Han, Meifang, Wan, Xiaoyang, Kilonzo, Semvua Bukheti, Luo, Xiaoping, Chen, Tao, Ning, Qin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019787/
https://www.ncbi.nlm.nih.gov/pubmed/29940856
http://dx.doi.org/10.1186/s12865-018-0256-x
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author Zhang, Xiaoping
Zhu, Lin
Zhou, Yaoyong
Shi, Aichao
Wang, Hongwu
Han, Meifang
Wan, Xiaoyang
Kilonzo, Semvua Bukheti
Luo, Xiaoping
Chen, Tao
Ning, Qin
author_facet Zhang, Xiaoping
Zhu, Lin
Zhou, Yaoyong
Shi, Aichao
Wang, Hongwu
Han, Meifang
Wan, Xiaoyang
Kilonzo, Semvua Bukheti
Luo, Xiaoping
Chen, Tao
Ning, Qin
author_sort Zhang, Xiaoping
collection PubMed
description BACKGROUND: Potassium channel tetramerisation domain containing 9 (KCTD9), a member of KCTD family with a DNA-like pentapeptide repeat domain, was found to be increased particularly in NK cells of patients with HBV-induced acute-on-chronic liver failure (HBV-ACLF) and experimental viral fulminant hepatitis. Knockdown of KCTD9 in immortalized NK cells inhibits cytokines production and cytotoxicity. As NK cell activation was shown to exacerbate liver damage in viral fulminant hepatitis, we propose that target inhibition of KCTD9 may prohibit NK cells activity and thus ameliorate liver damage in viral fulminant hepatitis. RESULT: Hydrodynamic delivery of plasmid expressing short-hairpin RNA against KCTD9 resulted in impaired NK cells function as demonstrated by reduced cytokine production and cytotoxicity, and ameliorated liver injury as manifested by improved liver histology and survival rate. In contrast, delivery of plasmid expressing KCTD9 led to deteriorated disease progression. CONCLUSION: Interference with KCTD9 expression exert beneficial effect in viral fulminant hepatitis therapy. Such effect may be mediated by impairment of NK cell activation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12865-018-0256-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-60197872018-07-06 Interference with KCTD9 inhibits NK cell activation and ameliorates fulminant liver failure in mice Zhang, Xiaoping Zhu, Lin Zhou, Yaoyong Shi, Aichao Wang, Hongwu Han, Meifang Wan, Xiaoyang Kilonzo, Semvua Bukheti Luo, Xiaoping Chen, Tao Ning, Qin BMC Immunol Research Article BACKGROUND: Potassium channel tetramerisation domain containing 9 (KCTD9), a member of KCTD family with a DNA-like pentapeptide repeat domain, was found to be increased particularly in NK cells of patients with HBV-induced acute-on-chronic liver failure (HBV-ACLF) and experimental viral fulminant hepatitis. Knockdown of KCTD9 in immortalized NK cells inhibits cytokines production and cytotoxicity. As NK cell activation was shown to exacerbate liver damage in viral fulminant hepatitis, we propose that target inhibition of KCTD9 may prohibit NK cells activity and thus ameliorate liver damage in viral fulminant hepatitis. RESULT: Hydrodynamic delivery of plasmid expressing short-hairpin RNA against KCTD9 resulted in impaired NK cells function as demonstrated by reduced cytokine production and cytotoxicity, and ameliorated liver injury as manifested by improved liver histology and survival rate. In contrast, delivery of plasmid expressing KCTD9 led to deteriorated disease progression. CONCLUSION: Interference with KCTD9 expression exert beneficial effect in viral fulminant hepatitis therapy. Such effect may be mediated by impairment of NK cell activation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12865-018-0256-x) contains supplementary material, which is available to authorized users. BioMed Central 2018-06-25 /pmc/articles/PMC6019787/ /pubmed/29940856 http://dx.doi.org/10.1186/s12865-018-0256-x Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zhang, Xiaoping
Zhu, Lin
Zhou, Yaoyong
Shi, Aichao
Wang, Hongwu
Han, Meifang
Wan, Xiaoyang
Kilonzo, Semvua Bukheti
Luo, Xiaoping
Chen, Tao
Ning, Qin
Interference with KCTD9 inhibits NK cell activation and ameliorates fulminant liver failure in mice
title Interference with KCTD9 inhibits NK cell activation and ameliorates fulminant liver failure in mice
title_full Interference with KCTD9 inhibits NK cell activation and ameliorates fulminant liver failure in mice
title_fullStr Interference with KCTD9 inhibits NK cell activation and ameliorates fulminant liver failure in mice
title_full_unstemmed Interference with KCTD9 inhibits NK cell activation and ameliorates fulminant liver failure in mice
title_short Interference with KCTD9 inhibits NK cell activation and ameliorates fulminant liver failure in mice
title_sort interference with kctd9 inhibits nk cell activation and ameliorates fulminant liver failure in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019787/
https://www.ncbi.nlm.nih.gov/pubmed/29940856
http://dx.doi.org/10.1186/s12865-018-0256-x
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