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...

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Autores principales:	Jinxiang Wu, Jintao Zhang, Jiping Zhao, Shihong Chen, Tao Zhou, Jianwei Xu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	severe acute pancreatitis acute lung injury pyroptosis GSDMD disulfiram programmed cell death Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/46512b7b269840048b5551bcdfe27463
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spelling	oai:doaj.org-article:46512b7b269840048b5551bcdfe274632021-11-11T09:58:40ZTreatment of Severe Acute Pancreatitis and Related Lung Injury by Targeting Gasdermin D-Mediated Pyroptosis2296-634X10.3389/fcell.2021.780142https://doaj.org/article/46512b7b269840048b5551bcdfe274632021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.780142/fullhttps://doaj.org/toc/2296-634XThe 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.Jinxiang WuJintao ZhangJiping ZhaoShihong ChenTao ZhouJianwei XuFrontiers Media S.A.articlesevere acute pancreatitisacute lung injurypyroptosisGSDMDdisulfiramprogrammed cell deathBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	severe acute pancreatitis acute lung injury pyroptosis GSDMD disulfiram programmed cell death Biology (General) QH301-705.5
spellingShingle	severe acute pancreatitis acute lung injury pyroptosis GSDMD disulfiram programmed cell death Biology (General) QH301-705.5 Jinxiang Wu Jintao Zhang Jiping Zhao Shihong Chen Tao Zhou Jianwei Xu Treatment of Severe Acute Pancreatitis and Related Lung Injury by Targeting Gasdermin D-Mediated Pyroptosis
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	article
author	Jinxiang Wu Jintao Zhang Jiping Zhao Shihong Chen Tao Zhou Jianwei Xu
author_facet	Jinxiang Wu Jintao Zhang Jiping Zhao Shihong Chen Tao Zhou Jianwei Xu
author_sort	Jinxiang Wu
title	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_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_sort	treatment of severe acute pancreatitis and related lung injury by targeting gasdermin d-mediated pyroptosis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/46512b7b269840048b5551bcdfe27463
work_keys_str_mv	AT jinxiangwu treatmentofsevereacutepancreatitisandrelatedlunginjurybytargetinggasdermindmediatedpyroptosis AT jintaozhang treatmentofsevereacutepancreatitisandrelatedlunginjurybytargetinggasdermindmediatedpyroptosis AT jipingzhao treatmentofsevereacutepancreatitisandrelatedlunginjurybytargetinggasdermindmediatedpyroptosis AT shihongchen treatmentofsevereacutepancreatitisandrelatedlunginjurybytargetinggasdermindmediatedpyroptosis AT taozhou treatmentofsevereacutepancreatitisandrelatedlunginjurybytargetinggasdermindmediatedpyroptosis AT jianweixu treatmentofsevereacutepancreatitisandrelatedlunginjurybytargetinggasdermindmediatedpyroptosis
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Treatment of Severe Acute Pancreatitis and Related Lung Injury by Targeting Gasdermin D-Mediated Pyroptosis

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