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TLR9 Mediates Remote Liver Injury following Severe Renal Ischemia Reperfusion
Ischemia reperfusion injury is a common cause of acute kidney injury and is characterized by tubular damage. Mitochondrial DNA is released upon severe tissue injury and can act as a damage-associated molecular pattern via the innate immune receptor TLR9. Here, we investigated the role of TLR9 in the...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567139/ https://www.ncbi.nlm.nih.gov/pubmed/26361210 http://dx.doi.org/10.1371/journal.pone.0137511 |
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author | Bakker, Pieter J. Scantlebery, Angelique M. Butter, Loes M. Claessen, Nike Teske, Gwendoline J. D. van der Poll, Tom Florquin, Sandrine Leemans, Jaklien C. |
author_facet | Bakker, Pieter J. Scantlebery, Angelique M. Butter, Loes M. Claessen, Nike Teske, Gwendoline J. D. van der Poll, Tom Florquin, Sandrine Leemans, Jaklien C. |
author_sort | Bakker, Pieter J. |
collection | PubMed |
description | Ischemia reperfusion injury is a common cause of acute kidney injury and is characterized by tubular damage. Mitochondrial DNA is released upon severe tissue injury and can act as a damage-associated molecular pattern via the innate immune receptor TLR9. Here, we investigated the role of TLR9 in the context of moderate or severe renal ischemia reperfusion injury using wild-type C57BL/6 mice or TLR9KO mice. Moderate renal ischemia induced renal dysfunction but did not decrease animal well-being and was not regulated by TLR9. In contrast, severe renal ischemia decreased animal well-being and survival in wild-type mice after respectively one or five days of reperfusion. TLR9 deficiency improved animal well-being and survival. TLR9 deficiency did not reduce renal inflammation or tubular necrosis. Rather, severe renal ischemia induced hepatic injury as seen by increased plasma ALAT and ASAT levels and focal hepatic necrosis which was prevented by TLR9 deficiency and correlated with reduced circulating mitochondrial DNA levels and plasma LDH. We conclude that TLR9 does not mediate renal dysfunction following either moderate or severe renal ischemia. In contrast, our data indicates that TLR9 is an important mediator of hepatic injury secondary to ischemic acute kidney injury. |
format | Online Article Text |
id | pubmed-4567139 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45671392015-09-18 TLR9 Mediates Remote Liver Injury following Severe Renal Ischemia Reperfusion Bakker, Pieter J. Scantlebery, Angelique M. Butter, Loes M. Claessen, Nike Teske, Gwendoline J. D. van der Poll, Tom Florquin, Sandrine Leemans, Jaklien C. PLoS One Research Article Ischemia reperfusion injury is a common cause of acute kidney injury and is characterized by tubular damage. Mitochondrial DNA is released upon severe tissue injury and can act as a damage-associated molecular pattern via the innate immune receptor TLR9. Here, we investigated the role of TLR9 in the context of moderate or severe renal ischemia reperfusion injury using wild-type C57BL/6 mice or TLR9KO mice. Moderate renal ischemia induced renal dysfunction but did not decrease animal well-being and was not regulated by TLR9. In contrast, severe renal ischemia decreased animal well-being and survival in wild-type mice after respectively one or five days of reperfusion. TLR9 deficiency improved animal well-being and survival. TLR9 deficiency did not reduce renal inflammation or tubular necrosis. Rather, severe renal ischemia induced hepatic injury as seen by increased plasma ALAT and ASAT levels and focal hepatic necrosis which was prevented by TLR9 deficiency and correlated with reduced circulating mitochondrial DNA levels and plasma LDH. We conclude that TLR9 does not mediate renal dysfunction following either moderate or severe renal ischemia. In contrast, our data indicates that TLR9 is an important mediator of hepatic injury secondary to ischemic acute kidney injury. Public Library of Science 2015-09-11 /pmc/articles/PMC4567139/ /pubmed/26361210 http://dx.doi.org/10.1371/journal.pone.0137511 Text en © 2015 Bakker et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Bakker, Pieter J. Scantlebery, Angelique M. Butter, Loes M. Claessen, Nike Teske, Gwendoline J. D. van der Poll, Tom Florquin, Sandrine Leemans, Jaklien C. TLR9 Mediates Remote Liver Injury following Severe Renal Ischemia Reperfusion |
title | TLR9 Mediates Remote Liver Injury following Severe Renal Ischemia Reperfusion |
title_full | TLR9 Mediates Remote Liver Injury following Severe Renal Ischemia Reperfusion |
title_fullStr | TLR9 Mediates Remote Liver Injury following Severe Renal Ischemia Reperfusion |
title_full_unstemmed | TLR9 Mediates Remote Liver Injury following Severe Renal Ischemia Reperfusion |
title_short | TLR9 Mediates Remote Liver Injury following Severe Renal Ischemia Reperfusion |
title_sort | tlr9 mediates remote liver injury following severe renal ischemia reperfusion |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567139/ https://www.ncbi.nlm.nih.gov/pubmed/26361210 http://dx.doi.org/10.1371/journal.pone.0137511 |
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