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Treatment of Severe Acute Pancreatitis and Related Lung Injury by Targeting Gasdermin D-Mediated Pyroptosis
The functional relevance and effects of the pyroptosis executioner gasdermin D (GSDMD) on severe acute pancreatitis (SAP)-associated lung injury are unclear. We established caerulein-induced mouse models of SAP-associated lung injury, which showed that GSDMD-mediated pyroptosis was activated in both...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632453/ https://www.ncbi.nlm.nih.gov/pubmed/34858995 http://dx.doi.org/10.3389/fcell.2021.780142 |
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author | Wu, Jinxiang Zhang, Jintao Zhao, Jiping Chen, Shihong Zhou, Tao Xu, Jianwei |
author_facet | Wu, Jinxiang Zhang, Jintao Zhao, Jiping Chen, Shihong Zhou, Tao Xu, Jianwei |
author_sort | Wu, Jinxiang |
collection | PubMed |
description | The functional relevance and effects of the pyroptosis executioner gasdermin D (GSDMD) on severe acute pancreatitis (SAP)-associated lung injury are unclear. We established caerulein-induced mouse models of SAP-associated lung injury, which showed that GSDMD-mediated pyroptosis was activated in both pancreatic and lung tissues. Compared with Gsdmd wild-type SAP mouse models, Gsdmd knockout (Gsdmd(–/–)) ameliorated SAP-induced pancreas and related lung injury. Additionally, we investigated the effects of disulfiram on the treatment of SAP. Disulfiram is a Food and Drug Administration (FDA)-approved anti-alcoholism drug, which is reported as an effective pyroptosis inhibitor by either directly covalently modifying GSDMD or indirectly inhibiting the cleavage of GSDMD via inactivating Nod-like receptor protein 3 inflammasome. We demonstrated that disulfiram inhibited the cleavage of GSDMD, alleviated caerulein-induced SAP and related lung injury, and decreased the expression levels of proinflammatory cytokines (IL-1β and IL-18). Collectively, these findings disclosed the role of GSDMD-mediated pyroptosis in SAP and the potential application of disulfiram in the treatment of SAP. |
format | Online Article Text |
id | pubmed-8632453 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86324532021-12-01 Treatment of Severe Acute Pancreatitis and Related Lung Injury by Targeting Gasdermin D-Mediated Pyroptosis Wu, Jinxiang Zhang, Jintao Zhao, Jiping Chen, Shihong Zhou, Tao Xu, Jianwei Front Cell Dev Biol Cell and Developmental Biology The functional relevance and effects of the pyroptosis executioner gasdermin D (GSDMD) on severe acute pancreatitis (SAP)-associated lung injury are unclear. We established caerulein-induced mouse models of SAP-associated lung injury, which showed that GSDMD-mediated pyroptosis was activated in both pancreatic and lung tissues. Compared with Gsdmd wild-type SAP mouse models, Gsdmd knockout (Gsdmd(–/–)) ameliorated SAP-induced pancreas and related lung injury. Additionally, we investigated the effects of disulfiram on the treatment of SAP. Disulfiram is a Food and Drug Administration (FDA)-approved anti-alcoholism drug, which is reported as an effective pyroptosis inhibitor by either directly covalently modifying GSDMD or indirectly inhibiting the cleavage of GSDMD via inactivating Nod-like receptor protein 3 inflammasome. We demonstrated that disulfiram inhibited the cleavage of GSDMD, alleviated caerulein-induced SAP and related lung injury, and decreased the expression levels of proinflammatory cytokines (IL-1β and IL-18). Collectively, these findings disclosed the role of GSDMD-mediated pyroptosis in SAP and the potential application of disulfiram in the treatment of SAP. Frontiers Media S.A. 2021-11-11 /pmc/articles/PMC8632453/ /pubmed/34858995 http://dx.doi.org/10.3389/fcell.2021.780142 Text en Copyright © 2021 Wu, Zhang, Zhao, Chen, Zhou and Xu. https://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 | Cell and Developmental Biology Wu, Jinxiang Zhang, Jintao Zhao, Jiping Chen, Shihong Zhou, Tao Xu, Jianwei Treatment of Severe Acute Pancreatitis and Related Lung Injury by Targeting Gasdermin D-Mediated Pyroptosis |
title | Treatment of Severe Acute Pancreatitis and Related Lung Injury by Targeting Gasdermin D-Mediated Pyroptosis |
title_full | Treatment of Severe Acute Pancreatitis and Related Lung Injury by Targeting Gasdermin D-Mediated Pyroptosis |
title_fullStr | Treatment of Severe Acute Pancreatitis and Related Lung Injury by Targeting Gasdermin D-Mediated Pyroptosis |
title_full_unstemmed | Treatment of Severe Acute Pancreatitis and Related Lung Injury by Targeting Gasdermin D-Mediated Pyroptosis |
title_short | Treatment of Severe Acute Pancreatitis and Related Lung Injury by Targeting Gasdermin D-Mediated Pyroptosis |
title_sort | treatment of severe acute pancreatitis and related lung injury by targeting gasdermin d-mediated pyroptosis |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632453/ https://www.ncbi.nlm.nih.gov/pubmed/34858995 http://dx.doi.org/10.3389/fcell.2021.780142 |
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