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Alcohol-Induced Liver Injury Is Modulated by Nlrp3 and Nlrc4 Inflammasomes in Mice
Alcoholic liver disease (ALD) is characterized by increased hepatic lipid accumulation (steatosis) and inflammation with increased expression of proinflammatory cytokines. Two of these cytokines, interleukin-1β (IL-1β) and IL-18, require activation of caspase-1 via members of the NOD-like receptor (...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876912/ https://www.ncbi.nlm.nih.gov/pubmed/24453428 http://dx.doi.org/10.1155/2013/751374 |
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author | DeSantis, David A. Ko, Chih-wei Liu, Yang Liu, Xiuli Hise, Amy G. Nunez, Gabriel Croniger, Colleen M. |
author_facet | DeSantis, David A. Ko, Chih-wei Liu, Yang Liu, Xiuli Hise, Amy G. Nunez, Gabriel Croniger, Colleen M. |
author_sort | DeSantis, David A. |
collection | PubMed |
description | Alcoholic liver disease (ALD) is characterized by increased hepatic lipid accumulation (steatosis) and inflammation with increased expression of proinflammatory cytokines. Two of these cytokines, interleukin-1β (IL-1β) and IL-18, require activation of caspase-1 via members of the NOD-like receptor (NLR) family. These NLRs form an inflammasome that is activated by pathogens and signals released through local tissue injury or death. NLR family pyrin domain containing 3 (Nlrp3) and NLR family CARD domain containing protein 4 (Nlrc4) have been studied minimally for their role in the development of ALD. Using mice with gene targeted deletions for Nlrp3 (Nlrp3(−/−)) and Nlrc4 (Nlrc4(−/−)), we analyzed the response to chronic alcohol consumption. We found that Nlrp3(−/−) mice have more severe liver injury with higher plasma alanine aminotransferase (ALT) levels, increased activation of IL-18, and reduced activation of IL-1B. In contrast, the Nlrc4(−/−) mice had similar alcohol-induced liver injury compared to C57BL/6J (B6) mice but had greatly reduced activation of IL-1β. This suggests that Nlrp3 and Nlrc4 inflammasomes activate IL-1β and IL-18 via caspase-1 in a differential manner. We conclude that the Nlrp3 inflammasome is protective during alcohol-induced liver injury. |
format | Online Article Text |
id | pubmed-3876912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-38769122014-01-16 Alcohol-Induced Liver Injury Is Modulated by Nlrp3 and Nlrc4 Inflammasomes in Mice DeSantis, David A. Ko, Chih-wei Liu, Yang Liu, Xiuli Hise, Amy G. Nunez, Gabriel Croniger, Colleen M. Mediators Inflamm Research Article Alcoholic liver disease (ALD) is characterized by increased hepatic lipid accumulation (steatosis) and inflammation with increased expression of proinflammatory cytokines. Two of these cytokines, interleukin-1β (IL-1β) and IL-18, require activation of caspase-1 via members of the NOD-like receptor (NLR) family. These NLRs form an inflammasome that is activated by pathogens and signals released through local tissue injury or death. NLR family pyrin domain containing 3 (Nlrp3) and NLR family CARD domain containing protein 4 (Nlrc4) have been studied minimally for their role in the development of ALD. Using mice with gene targeted deletions for Nlrp3 (Nlrp3(−/−)) and Nlrc4 (Nlrc4(−/−)), we analyzed the response to chronic alcohol consumption. We found that Nlrp3(−/−) mice have more severe liver injury with higher plasma alanine aminotransferase (ALT) levels, increased activation of IL-18, and reduced activation of IL-1B. In contrast, the Nlrc4(−/−) mice had similar alcohol-induced liver injury compared to C57BL/6J (B6) mice but had greatly reduced activation of IL-1β. This suggests that Nlrp3 and Nlrc4 inflammasomes activate IL-1β and IL-18 via caspase-1 in a differential manner. We conclude that the Nlrp3 inflammasome is protective during alcohol-induced liver injury. Hindawi Publishing Corporation 2013 2013-12-16 /pmc/articles/PMC3876912/ /pubmed/24453428 http://dx.doi.org/10.1155/2013/751374 Text en Copyright © 2013 David A. DeSantis et al. https://creativecommons.org/licenses/by/3.0/ 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 DeSantis, David A. Ko, Chih-wei Liu, Yang Liu, Xiuli Hise, Amy G. Nunez, Gabriel Croniger, Colleen M. Alcohol-Induced Liver Injury Is Modulated by Nlrp3 and Nlrc4 Inflammasomes in Mice |
title | Alcohol-Induced Liver Injury Is Modulated by Nlrp3 and Nlrc4 Inflammasomes in Mice |
title_full | Alcohol-Induced Liver Injury Is Modulated by Nlrp3 and Nlrc4 Inflammasomes in Mice |
title_fullStr | Alcohol-Induced Liver Injury Is Modulated by Nlrp3 and Nlrc4 Inflammasomes in Mice |
title_full_unstemmed | Alcohol-Induced Liver Injury Is Modulated by Nlrp3 and Nlrc4 Inflammasomes in Mice |
title_short | Alcohol-Induced Liver Injury Is Modulated by Nlrp3 and Nlrc4 Inflammasomes in Mice |
title_sort | alcohol-induced liver injury is modulated by nlrp3 and nlrc4 inflammasomes in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876912/ https://www.ncbi.nlm.nih.gov/pubmed/24453428 http://dx.doi.org/10.1155/2013/751374 |
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