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Compound loss of GSDMD and GSDME function is necessary to achieve maximal therapeutic effect in colitis

Gasdermin D (GSDMD) and gasdermin E (GSDME) perpetuate inflammation by mediating the release of cytokines such as interleukin-1β (IL-1β) and IL-18. However, not only are the actions of GSDMD in colitis still controversial, but its interplay with GSDME in the pathogenesis of this disease has not been...

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Autores principales: Xiao, Jianqiu, Sun, Kai, Wang, Chun, Abu-Amer, Yousef, Mbalaviele, Gabriel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463374/
https://www.ncbi.nlm.nih.gov/pubmed/36097634
http://dx.doi.org/10.1016/j.jtauto.2022.100162
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author Xiao, Jianqiu
Sun, Kai
Wang, Chun
Abu-Amer, Yousef
Mbalaviele, Gabriel
author_facet Xiao, Jianqiu
Sun, Kai
Wang, Chun
Abu-Amer, Yousef
Mbalaviele, Gabriel
author_sort Xiao, Jianqiu
collection PubMed
description Gasdermin D (GSDMD) and gasdermin E (GSDME) perpetuate inflammation by mediating the release of cytokines such as interleukin-1β (IL-1β) and IL-18. However, not only are the actions of GSDMD in colitis still controversial, but its interplay with GSDME in the pathogenesis of this disease has not been investigated. We sought to fill these knowledge gaps using the dextran sodium sulfate (DSS) experimental mouse colitis model. DSS ingestion by wild-type mice caused body weight loss as the result of severe gut inflammation, outcomes that were significantly attenuated in Gsdmd(−/−) or Gsdme(−/−) mice and nearly fully prevented in Gsdmd(−/−);Gsdme(−/−) animals. To assess the translational implications of these findings, we tested the efficacy of the active metabolite of US Food and Drug Administration (FDA)-approved disulfiram, which inhibits GSDMD and GSDME function. The severe DSS-induced gut toxicity was significantly decreased in mice treated with the inhibitor. Collectively, our findings indicate that disruption of the function of both GSDMD and GSDME is necessary to achieve maximal therapeutic effect in colitis.
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spelling pubmed-94633742022-09-11 Compound loss of GSDMD and GSDME function is necessary to achieve maximal therapeutic effect in colitis Xiao, Jianqiu Sun, Kai Wang, Chun Abu-Amer, Yousef Mbalaviele, Gabriel J Transl Autoimmun Editorial Gasdermin D (GSDMD) and gasdermin E (GSDME) perpetuate inflammation by mediating the release of cytokines such as interleukin-1β (IL-1β) and IL-18. However, not only are the actions of GSDMD in colitis still controversial, but its interplay with GSDME in the pathogenesis of this disease has not been investigated. We sought to fill these knowledge gaps using the dextran sodium sulfate (DSS) experimental mouse colitis model. DSS ingestion by wild-type mice caused body weight loss as the result of severe gut inflammation, outcomes that were significantly attenuated in Gsdmd(−/−) or Gsdme(−/−) mice and nearly fully prevented in Gsdmd(−/−);Gsdme(−/−) animals. To assess the translational implications of these findings, we tested the efficacy of the active metabolite of US Food and Drug Administration (FDA)-approved disulfiram, which inhibits GSDMD and GSDME function. The severe DSS-induced gut toxicity was significantly decreased in mice treated with the inhibitor. Collectively, our findings indicate that disruption of the function of both GSDMD and GSDME is necessary to achieve maximal therapeutic effect in colitis. Elsevier 2022-08-30 /pmc/articles/PMC9463374/ /pubmed/36097634 http://dx.doi.org/10.1016/j.jtauto.2022.100162 Text en © 2022 The Authors. Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Editorial
Xiao, Jianqiu
Sun, Kai
Wang, Chun
Abu-Amer, Yousef
Mbalaviele, Gabriel
Compound loss of GSDMD and GSDME function is necessary to achieve maximal therapeutic effect in colitis
title Compound loss of GSDMD and GSDME function is necessary to achieve maximal therapeutic effect in colitis
title_full Compound loss of GSDMD and GSDME function is necessary to achieve maximal therapeutic effect in colitis
title_fullStr Compound loss of GSDMD and GSDME function is necessary to achieve maximal therapeutic effect in colitis
title_full_unstemmed Compound loss of GSDMD and GSDME function is necessary to achieve maximal therapeutic effect in colitis
title_short Compound loss of GSDMD and GSDME function is necessary to achieve maximal therapeutic effect in colitis
title_sort compound loss of gsdmd and gsdme function is necessary to achieve maximal therapeutic effect in colitis
topic Editorial
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463374/
https://www.ncbi.nlm.nih.gov/pubmed/36097634
http://dx.doi.org/10.1016/j.jtauto.2022.100162
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