Glucocorticoids limit lipopolysaccharide-induced lethal inflammation by a double control system.
TNF
glucocorticoids
lipopolysaccharides
systemic inflammatory response syndrome
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
03 07 2020
03 07 2020
Historique:
received:
27
11
2019
revised:
10
04
2020
accepted:
15
04
2020
pubmed:
10
5
2020
medline:
28
4
2021
entrez:
9
5
2020
Statut:
ppublish
Résumé
Lipopolysaccharides (LPS) can lead to a lethal endotoxemia, which is a systemic inflammatory response syndrome (SIRS) characterized by a systemic release of cytokines, such as TNF. Endotoxemia is studied intensely, as a model system of Gram-negative infections. LPS- and TNF-induced SIRS involve a strong induction of interferon-stimulated genes (ISGs), some of which cause cell death in the intestinal epithelium cells (IECs). It is well known that glucocorticoids (GCs) protect against endotoxemia. By applying numerous mutant mouse lines, our data support a model whereby GCs, via their glucocorticoid receptor (GR), apply two key mechanisms to control endotoxemia, (i) at the level of suppression of TNF production in a GR monomer-dependent way in macrophages and (ii) at the level of inhibition of TNFR1-induced ISG gene expression and necroptotic cell death mediators in IECs in a GR dimer-dependent way. Our data add new important insights to the understanding of the role of TNF in endotoxemia and the two separate key roles of GCs in suppressing TNF production and activity.
Identifiants
pubmed: 32383538
doi: 10.15252/embr.201949762
pmc: PMC7332980
doi:
Substances chimiques
Cytokines
0
Glucocorticoids
0
Lipopolysaccharides
0
Tumor Necrosis Factor-alpha
0
Banques de données
GEO
['GSE113691', 'GSE139903']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e49762Subventions
Organisme : Fonds Wetenschappelijk Onderzoek (FWO)
ID : G006616N
Pays : International
Organisme : Universiteit Gent (UGent)
ID : BOF19-GOA-004-1
Pays : International
Organisme : Vlaams Instituut voor Biotechnologie (VIB)
ID : DOTATION-LIBERT-2017-2021
Pays : International
Informations de copyright
© 2020 The Authors.
Références
Trends Endocrinol Metab. 2018 Jan;29(1):42-54
pubmed: 29162310
Cell. 2011 Apr 15;145(2):224-41
pubmed: 21496643
Nucleic Acids Res. 2013 Jan;41(Database issue):D1040-6
pubmed: 23203888
Blood. 2007 May 15;109(10):4313-9
pubmed: 17255352
Nat Immunol. 2008 Apr;9(4):378-87
pubmed: 18345002
Nat Immunol. 2012 Oct;13(10):954-62
pubmed: 22922364
J Clin Invest. 2012 Jun;122(6):2130-40
pubmed: 22585571
Nature. 2011 Jul 31;477(7364):330-4
pubmed: 21804564
Nat Rev Immunol. 2003 Feb;3(2):169-76
pubmed: 12563300
Nat Rev Mol Cell Biol. 2017 Feb;18(2):127-136
pubmed: 27999438
Nat Protoc. 2016 Sep;11(9):1650-67
pubmed: 27560171
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
pubmed: 12184808
Cell Death Differ. 2019 Jan;26(2):332-347
pubmed: 29786074
Gut. 2015 Apr;64(4):601-10
pubmed: 25379949
J Endotoxin Res. 2001;7(4):277-80
pubmed: 11717581
Mediators Inflamm. 2015;2015:250762
pubmed: 26483605
Curr Opin Genet Dev. 1998 Oct;8(5):532-8
pubmed: 9794823
Cell. 2014 May 22;157(5):1189-202
pubmed: 24813850
Trends Pharmacol Sci. 2016 Jan;37(1):4-16
pubmed: 26603477
Nature. 2011 Sep 14;477(7364):335-9
pubmed: 21921917
Cell Mol Immunol. 2020 Apr;17(4):356-368
pubmed: 31076724
J Exp Med. 2014 Jun 30;211(7):1393-405
pubmed: 24980747
FASEB J. 2012 Feb;26(2):722-9
pubmed: 22042221
Mol Psychiatry. 2013 Sep;18(9):1006-17
pubmed: 23089634
EMBO Rep. 2020 Jul 3;21(7):e49762
pubmed: 32383538
Int J Mol Sci. 2019 Apr 16;20(8):
pubmed: 30995806
J Clin Invest. 2018 Aug 1;128(8):3265-3279
pubmed: 29746256
Mol Cell Endocrinol. 2007 Sep 15;275(1-2):98-108
pubmed: 17587493
J Immunol. 1998 Jan 15;160(2):943-52
pubmed: 9551933
Nature. 2016 Dec 1;540(7631):124-128
pubmed: 27819681
Cell. 2012 Jan 20;148(1-2):213-27
pubmed: 22265413
Semin Cell Dev Biol. 2014 Nov;35:2-13
pubmed: 25160988
Dis Model Mech. 2013 Nov;6(6):1388-99
pubmed: 24046352
Cell Death Differ. 2016 Sep 1;23(9):1565-76
pubmed: 27177019
J Clin Invest. 2013 Jun;123(6):2590-603
pubmed: 23676465
J Biol Chem. 2011 Jul 29;286(30):26555-67
pubmed: 21646349
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
Gastroenterology. 2019 Nov;157(5):1310-1322.e13
pubmed: 31352002
Mucosal Immunol. 2015 Jul;8(4):828-40
pubmed: 25425265
Gene. 1999 Nov 15;240(1):157-63
pubmed: 10564822
EMBO Mol Med. 2015 May 20;7(8):1004-17
pubmed: 25995337
Physiol Rev. 2018 Apr 1;98(2):727-780
pubmed: 29465288
Cell Death Differ. 2016 Jan;23(1):76-88
pubmed: 26024392
Science. 1998 Dec 11;282(5396):2085-8
pubmed: 9851930
Surg Infect (Larchmt). 2016 Aug;17(4):385-93
pubmed: 27305321
Cell. 1998 May 15;93(4):531-41
pubmed: 9604929
Expert Opin Ther Targets. 2018 Dec;22(12):1029-1037
pubmed: 30343600
Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):E3109-18
pubmed: 23898178