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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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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. |
format | Online Article Text |
id | pubmed-9463374 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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