Zinc inhibits lethal inflammatory shock by preventing microbe‐induced interferon signature in intestinal epithelium
Abstract The cytokine TNF drives inflammatory diseases, e.g., Crohn's disease. In a mouse model of TNF‐induced systemic inflammatory response syndrome (SIRS), severe impact on intestinal epithelial cells (IECs) is observed. Zinc confers complete protection in this model. We found that zinc no l...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2020-10-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201911917 |
| _version_ | 1797281805014925312 |
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| author | Jolien Souffriau Steven Timmermans Tineke Vanderhaeghen Charlotte Wallaeys Kelly Van Looveren Lindsy Aelbrecht Sylviane Dewaele Jolien Vandewalle Evy Goossens Serge Verbanck Filip Boyen Melanie Eggermont Lindsey De Commer Riet De Rycke Michiel De Bruyne Raul Tito Marlies Ballegeer Sofie Vandevyver Tiago Velho Luis Ferreira Moita Tino Hochepied Karolien De Bosscher Jeroen Raes Filip Van Immerseel Rudi Beyaert Claude Libert |
| author_facet | Jolien Souffriau Steven Timmermans Tineke Vanderhaeghen Charlotte Wallaeys Kelly Van Looveren Lindsy Aelbrecht Sylviane Dewaele Jolien Vandewalle Evy Goossens Serge Verbanck Filip Boyen Melanie Eggermont Lindsey De Commer Riet De Rycke Michiel De Bruyne Raul Tito Marlies Ballegeer Sofie Vandevyver Tiago Velho Luis Ferreira Moita Tino Hochepied Karolien De Bosscher Jeroen Raes Filip Van Immerseel Rudi Beyaert Claude Libert |
| author_sort | Jolien Souffriau |
| collection | DOAJ |
| description | Abstract The cytokine TNF drives inflammatory diseases, e.g., Crohn's disease. In a mouse model of TNF‐induced systemic inflammatory response syndrome (SIRS), severe impact on intestinal epithelial cells (IECs) is observed. Zinc confers complete protection in this model. We found that zinc no longer protects in animals which lack glucocorticoids (GCs), or express mutant versions of their receptor GR in IECs, nor in mice which lack gut microbiota. RNA‐seq studies in IECs showed that zinc caused reduction in expression of constitutive (STAT1‐induced) interferon‐stimulated response (ISRE) genes and interferon regulatory factor (IRF) genes. Since some of these genes are involved in TNF‐induced cell death in intestinal crypt Paneth cells, and since zinc has direct effects on the composition of the gut microbiota (such as several Staphylococcus species) and on TNF‐induced Paneth cell death, we postulate a new zinc‐related anti‐inflammatory mechanism. Zinc modulates the gut microbiota, causing less induction of ISRE/IRF genes in crypt cells, less TNF‐induced necroptosis in Paneth cells, and less fatal evasion of gut bacteria into the system. |
| first_indexed | 2024-03-07T17:02:45Z |
| format | Article |
| id | doaj.art-3e993b5bbeaf4e78b2bc46c529806814 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T17:02:45Z |
| publishDate | 2020-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-3e993b5bbeaf4e78b2bc46c5298068142024-03-03T03:14:30ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842020-10-011210n/an/a10.15252/emmm.201911917Zinc inhibits lethal inflammatory shock by preventing microbe‐induced interferon signature in intestinal epitheliumJolien Souffriau0Steven Timmermans1Tineke Vanderhaeghen2Charlotte Wallaeys3Kelly Van Looveren4Lindsy Aelbrecht5Sylviane Dewaele6Jolien Vandewalle7Evy Goossens8Serge Verbanck9Filip Boyen10Melanie Eggermont11Lindsey De Commer12Riet De Rycke13Michiel De Bruyne14Raul Tito15Marlies Ballegeer16Sofie Vandevyver17Tiago Velho18Luis Ferreira Moita19Tino Hochepied20Karolien De Bosscher21Jeroen Raes22Filip Van Immerseel23Rudi Beyaert24Claude Libert25Center for Inflammation Research VIB Ghent BelgiumCenter for Inflammation Research VIB Ghent BelgiumCenter for Inflammation Research VIB Ghent BelgiumCenter for Inflammation Research VIB Ghent BelgiumCenter for Inflammation Research VIB Ghent BelgiumCenter for Inflammation Research VIB Ghent BelgiumCenter for Inflammation Research VIB Ghent BelgiumCenter for Inflammation Research VIB Ghent BelgiumDepartment of Pathology, Bacteriology and Avian Diseases Faculty of Veterinary Medicine Ghent University Merelbeke BelgiumDepartment of Pathology, Bacteriology and Avian Diseases Faculty of Veterinary Medicine Ghent University Merelbeke BelgiumDepartment of Pathology, Bacteriology and Avian Diseases Faculty of Veterinary Medicine Ghent University Merelbeke BelgiumCenter for Inflammation Research VIB Ghent BelgiumDepartment of Microbiology and Immunology Rega Institute, KU Leuven Leuven BelgiumDepartment of Biomedical Molecular Biology and Expertise Centre for Transmission Electron Microscopy Ghent University Ghent BelgiumDepartment of Biomedical Molecular Biology and Expertise Centre for Transmission Electron Microscopy Ghent University Ghent BelgiumDepartment of Microbiology and Immunology Rega Institute, KU Leuven Leuven BelgiumCenter for Inflammation Research VIB Ghent BelgiumCenter for Inflammation Research VIB Ghent BelgiumInstituto Gulbenkian de Ciência Oeiras PortugalInstituto Gulbenkian de Ciência Oeiras PortugalCenter for Inflammation Research VIB Ghent BelgiumVIB Center for Medical Biotechnology Ghent BelgiumDepartment of Microbiology and Immunology Rega Institute, KU Leuven Leuven BelgiumDepartment of Pathology, Bacteriology and Avian Diseases Faculty of Veterinary Medicine Ghent University Merelbeke BelgiumCenter for Inflammation Research VIB Ghent BelgiumCenter for Inflammation Research VIB Ghent BelgiumAbstract The cytokine TNF drives inflammatory diseases, e.g., Crohn's disease. In a mouse model of TNF‐induced systemic inflammatory response syndrome (SIRS), severe impact on intestinal epithelial cells (IECs) is observed. Zinc confers complete protection in this model. We found that zinc no longer protects in animals which lack glucocorticoids (GCs), or express mutant versions of their receptor GR in IECs, nor in mice which lack gut microbiota. RNA‐seq studies in IECs showed that zinc caused reduction in expression of constitutive (STAT1‐induced) interferon‐stimulated response (ISRE) genes and interferon regulatory factor (IRF) genes. Since some of these genes are involved in TNF‐induced cell death in intestinal crypt Paneth cells, and since zinc has direct effects on the composition of the gut microbiota (such as several Staphylococcus species) and on TNF‐induced Paneth cell death, we postulate a new zinc‐related anti‐inflammatory mechanism. Zinc modulates the gut microbiota, causing less induction of ISRE/IRF genes in crypt cells, less TNF‐induced necroptosis in Paneth cells, and less fatal evasion of gut bacteria into the system.https://doi.org/10.15252/emmm.201911917geneticsinflammationmicrobiotanutrientregulation |
| spellingShingle | Jolien Souffriau Steven Timmermans Tineke Vanderhaeghen Charlotte Wallaeys Kelly Van Looveren Lindsy Aelbrecht Sylviane Dewaele Jolien Vandewalle Evy Goossens Serge Verbanck Filip Boyen Melanie Eggermont Lindsey De Commer Riet De Rycke Michiel De Bruyne Raul Tito Marlies Ballegeer Sofie Vandevyver Tiago Velho Luis Ferreira Moita Tino Hochepied Karolien De Bosscher Jeroen Raes Filip Van Immerseel Rudi Beyaert Claude Libert Zinc inhibits lethal inflammatory shock by preventing microbe‐induced interferon signature in intestinal epithelium EMBO Molecular Medicine genetics inflammation microbiota nutrient regulation |
| title | Zinc inhibits lethal inflammatory shock by preventing microbe‐induced interferon signature in intestinal epithelium |
| title_full | Zinc inhibits lethal inflammatory shock by preventing microbe‐induced interferon signature in intestinal epithelium |
| title_fullStr | Zinc inhibits lethal inflammatory shock by preventing microbe‐induced interferon signature in intestinal epithelium |
| title_full_unstemmed | Zinc inhibits lethal inflammatory shock by preventing microbe‐induced interferon signature in intestinal epithelium |
| title_short | Zinc inhibits lethal inflammatory shock by preventing microbe‐induced interferon signature in intestinal epithelium |
| title_sort | zinc inhibits lethal inflammatory shock by preventing microbe induced interferon signature in intestinal epithelium |
| topic | genetics inflammation microbiota nutrient regulation |
| url | https://doi.org/10.15252/emmm.201911917 |
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