Zinc inhibits lethal inflammatory shock by preventing microbe-induced interferon signature in intestinal epithelium.
genetics
inflammation
microbiota
nutrient
regulation
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
07 10 2020
07 10 2020
Historique:
received:
18
12
2019
revised:
19
08
2020
accepted:
19
08
2020
pubmed:
12
9
2020
medline:
19
8
2021
entrez:
11
9
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32914580
doi: 10.15252/emmm.201911917
pmc: PMC7539219
doi:
Substances chimiques
Interferons
9008-11-1
Zinc
J41CSQ7QDS
Banques de données
GEO
['GSE156119', 'GSE156242', 'GSE156282']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e11917Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
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