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TNFα-Mediated Necroptosis Aggravates Ischemia-Reperfusion Injury in the Fatty Liver by Regulating the Inflammatory Response
Nonalcoholic fatty liver disease (NAFLD) is more sensitive to ischemia and reperfusion injury (IRI), while there are no effective methods to alleviate IRI. Necroptosis, also known as “programmed necrosis,” incorporates features of necrosis and apoptosis. However, the role of necroptosis in IRI of th...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535887/ https://www.ncbi.nlm.nih.gov/pubmed/31214277 http://dx.doi.org/10.1155/2019/2301903 |
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author | Yang, Faji Shang, Longcheng Wang, Shuai Liu, Yang Ren, Haozhen Zhu, Wei Shi, Xiaolei |
author_facet | Yang, Faji Shang, Longcheng Wang, Shuai Liu, Yang Ren, Haozhen Zhu, Wei Shi, Xiaolei |
author_sort | Yang, Faji |
collection | PubMed |
description | Nonalcoholic fatty liver disease (NAFLD) is more sensitive to ischemia and reperfusion injury (IRI), while there are no effective methods to alleviate IRI. Necroptosis, also known as “programmed necrosis,” incorporates features of necrosis and apoptosis. However, the role of necroptosis in IRI of the fatty liver remains largely unexplored. In the present study, we aimed to assess whether necroptosis was activated in the fatty liver and whether such activation accelerated IRI in the fatty liver. In this study, we found that the liver IRI was enhanced in HFD-fed mice with more release of TNFα. TNFα and supernatant of macrophages could induce necroptosis of hepatocytes in vitro. Necroptosis was activated in NAFLD, leading to more severe IRI, and such necroptosis could be inhibited by TN3-19.12, the neutralizing monoclonal antibody against TNFα. Pretreatment with Nec-1 and GSK′872, two inhibitors of necroptosis, significantly reduced the liver IRI and ROS production in HFD-fed mice. Moreover, the inhibition of necroptosis could decrease ROS production of hepatocytes in vitro. Inflammatory response was activated during IRI, and necroptosis inhibitors could suppress signaling pathways of inflammation and the soakage of inflammation cells. In conclusion, TNFα-induced necroptosis played an important role during IRI in the fatty liver. Our findings demonstrated that necroptosis might be a potential target to reduce the fatty liver-associated IRI. |
format | Online Article Text |
id | pubmed-6535887 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-65358872019-06-18 TNFα-Mediated Necroptosis Aggravates Ischemia-Reperfusion Injury in the Fatty Liver by Regulating the Inflammatory Response Yang, Faji Shang, Longcheng Wang, Shuai Liu, Yang Ren, Haozhen Zhu, Wei Shi, Xiaolei Oxid Med Cell Longev Research Article Nonalcoholic fatty liver disease (NAFLD) is more sensitive to ischemia and reperfusion injury (IRI), while there are no effective methods to alleviate IRI. Necroptosis, also known as “programmed necrosis,” incorporates features of necrosis and apoptosis. However, the role of necroptosis in IRI of the fatty liver remains largely unexplored. In the present study, we aimed to assess whether necroptosis was activated in the fatty liver and whether such activation accelerated IRI in the fatty liver. In this study, we found that the liver IRI was enhanced in HFD-fed mice with more release of TNFα. TNFα and supernatant of macrophages could induce necroptosis of hepatocytes in vitro. Necroptosis was activated in NAFLD, leading to more severe IRI, and such necroptosis could be inhibited by TN3-19.12, the neutralizing monoclonal antibody against TNFα. Pretreatment with Nec-1 and GSK′872, two inhibitors of necroptosis, significantly reduced the liver IRI and ROS production in HFD-fed mice. Moreover, the inhibition of necroptosis could decrease ROS production of hepatocytes in vitro. Inflammatory response was activated during IRI, and necroptosis inhibitors could suppress signaling pathways of inflammation and the soakage of inflammation cells. In conclusion, TNFα-induced necroptosis played an important role during IRI in the fatty liver. Our findings demonstrated that necroptosis might be a potential target to reduce the fatty liver-associated IRI. Hindawi 2019-05-12 /pmc/articles/PMC6535887/ /pubmed/31214277 http://dx.doi.org/10.1155/2019/2301903 Text en Copyright © 2019 Faji Yang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Yang, Faji Shang, Longcheng Wang, Shuai Liu, Yang Ren, Haozhen Zhu, Wei Shi, Xiaolei TNFα-Mediated Necroptosis Aggravates Ischemia-Reperfusion Injury in the Fatty Liver by Regulating the Inflammatory Response |
title | TNFα-Mediated Necroptosis Aggravates Ischemia-Reperfusion Injury in the Fatty Liver by Regulating the Inflammatory Response |
title_full | TNFα-Mediated Necroptosis Aggravates Ischemia-Reperfusion Injury in the Fatty Liver by Regulating the Inflammatory Response |
title_fullStr | TNFα-Mediated Necroptosis Aggravates Ischemia-Reperfusion Injury in the Fatty Liver by Regulating the Inflammatory Response |
title_full_unstemmed | TNFα-Mediated Necroptosis Aggravates Ischemia-Reperfusion Injury in the Fatty Liver by Regulating the Inflammatory Response |
title_short | TNFα-Mediated Necroptosis Aggravates Ischemia-Reperfusion Injury in the Fatty Liver by Regulating the Inflammatory Response |
title_sort | tnfα-mediated necroptosis aggravates ischemia-reperfusion injury in the fatty liver by regulating the inflammatory response |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535887/ https://www.ncbi.nlm.nih.gov/pubmed/31214277 http://dx.doi.org/10.1155/2019/2301903 |
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