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Card9 protects sepsis by regulating Ripk2-mediated activation of NLRP3 inflammasome in macrophages
Sepsis is characterized by systemic inflammation, it’s caused by primary infection of pathogenic microorganisms or secondary infection of damaged tissue. In this study, we focus on sepsis-induced intestine barrier functional disturbalice, presenting as increased permeability of intestinal epithelium...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135688/ https://www.ncbi.nlm.nih.gov/pubmed/35618701 http://dx.doi.org/10.1038/s41419-022-04938-y |
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author | Xu, Zhen Li, Daoqian Qu, Wei Yin, Yuxin Qiao, Shuping Zhu, Yanan Shen, Sunan Hou, Yayi Yang, Jie Wang, Tingting |
author_facet | Xu, Zhen Li, Daoqian Qu, Wei Yin, Yuxin Qiao, Shuping Zhu, Yanan Shen, Sunan Hou, Yayi Yang, Jie Wang, Tingting |
author_sort | Xu, Zhen |
collection | PubMed |
description | Sepsis is characterized by systemic inflammation, it’s caused by primary infection of pathogenic microorganisms or secondary infection of damaged tissue. In this study, we focus on sepsis-induced intestine barrier functional disturbalice, presenting as increased permeability of intestinal epithelium. We observed that the phenotype of LPS-induced sepsis was exacerbated in Card9(−/−) mice, especially displaying more serious intestinal inflammation and gut barrier dysfunction. Next, we found the hyperactivation of NLRP3 inflammasome in the intestinal macrophages of Card9(−/−)-sepsis mice. Moreover, Card9 over-expression decreased NLRP3 inflammasome activation in macrophages. Furthermore, we found that Card9 inhibited NLRP3 inflammasome activation by recruiting Ripk2. The competitive binding between Ripk2 with Caspase-1, instead of ASC with Caspase-1, inhibited the NLRP3 inflammasome activation. Over-expression of Ripk2 alleviated septic intestinal injury caused by Card9 deficiency. Taken together, we suggested Card9 acts as a negative regulation factor of NLRP3 inflammasome activation, which protects against intestinal damage during sepsis. Therefore, maintaining Card9-Ripk2 signaling homeostasis may provide a novel therapy of septic intestinal damage. |
format | Online Article Text |
id | pubmed-9135688 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91356882022-05-28 Card9 protects sepsis by regulating Ripk2-mediated activation of NLRP3 inflammasome in macrophages Xu, Zhen Li, Daoqian Qu, Wei Yin, Yuxin Qiao, Shuping Zhu, Yanan Shen, Sunan Hou, Yayi Yang, Jie Wang, Tingting Cell Death Dis Article Sepsis is characterized by systemic inflammation, it’s caused by primary infection of pathogenic microorganisms or secondary infection of damaged tissue. In this study, we focus on sepsis-induced intestine barrier functional disturbalice, presenting as increased permeability of intestinal epithelium. We observed that the phenotype of LPS-induced sepsis was exacerbated in Card9(−/−) mice, especially displaying more serious intestinal inflammation and gut barrier dysfunction. Next, we found the hyperactivation of NLRP3 inflammasome in the intestinal macrophages of Card9(−/−)-sepsis mice. Moreover, Card9 over-expression decreased NLRP3 inflammasome activation in macrophages. Furthermore, we found that Card9 inhibited NLRP3 inflammasome activation by recruiting Ripk2. The competitive binding between Ripk2 with Caspase-1, instead of ASC with Caspase-1, inhibited the NLRP3 inflammasome activation. Over-expression of Ripk2 alleviated septic intestinal injury caused by Card9 deficiency. Taken together, we suggested Card9 acts as a negative regulation factor of NLRP3 inflammasome activation, which protects against intestinal damage during sepsis. Therefore, maintaining Card9-Ripk2 signaling homeostasis may provide a novel therapy of septic intestinal damage. Nature Publishing Group UK 2022-05-26 /pmc/articles/PMC9135688/ /pubmed/35618701 http://dx.doi.org/10.1038/s41419-022-04938-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Xu, Zhen Li, Daoqian Qu, Wei Yin, Yuxin Qiao, Shuping Zhu, Yanan Shen, Sunan Hou, Yayi Yang, Jie Wang, Tingting Card9 protects sepsis by regulating Ripk2-mediated activation of NLRP3 inflammasome in macrophages |
title | Card9 protects sepsis by regulating Ripk2-mediated activation of NLRP3 inflammasome in macrophages |
title_full | Card9 protects sepsis by regulating Ripk2-mediated activation of NLRP3 inflammasome in macrophages |
title_fullStr | Card9 protects sepsis by regulating Ripk2-mediated activation of NLRP3 inflammasome in macrophages |
title_full_unstemmed | Card9 protects sepsis by regulating Ripk2-mediated activation of NLRP3 inflammasome in macrophages |
title_short | Card9 protects sepsis by regulating Ripk2-mediated activation of NLRP3 inflammasome in macrophages |
title_sort | card9 protects sepsis by regulating ripk2-mediated activation of nlrp3 inflammasome in macrophages |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135688/ https://www.ncbi.nlm.nih.gov/pubmed/35618701 http://dx.doi.org/10.1038/s41419-022-04938-y |
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