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Glucocorticoids limit lipopolysaccharide‐induced lethal inflammation by a double control system

Kelly Van Looveren (UGent) , Steven Timmermans (UGent) , Tineke Vanderhaeghen (UGent) , Charlotte Wallaeys (UGent) , Marlies Ballegeer (UGent) , Jolien Souffriau (UGent) , Melanie Eggermont (UGent) , Jolien Vandewalle (UGent) , Lise Van Wyngene (UGent) , Karolien De Bosscher (UGent) , et al.
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Abstract
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.
Keywords
Genetics, Biochemistry, Molecular Biology

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MLA
Van Looveren, Kelly, et al. “Glucocorticoids Limit Lipopolysaccharide‐induced Lethal Inflammation by a Double Control System.” EMBO REPORTS, 2020.
APA
Van Looveren, K., Timmermans, S., Vanderhaeghen, T., Wallaeys, C., Ballegeer, M., Souffriau, J., … Libert, C. (2020). Glucocorticoids limit lipopolysaccharide‐induced lethal inflammation by a double control system. EMBO REPORTS.
Chicago author-date
Van Looveren, Kelly, Steven Timmermans, Tineke Vanderhaeghen, Charlotte Wallaeys, Marlies Ballegeer, Jolien Souffriau, Melanie Eggermont, et al. 2020. “Glucocorticoids Limit Lipopolysaccharide‐induced Lethal Inflammation by a Double Control System.” EMBO REPORTS.
Chicago author-date (all authors)
Van Looveren, Kelly, Steven Timmermans, Tineke Vanderhaeghen, Charlotte Wallaeys, Marlies Ballegeer, Jolien Souffriau, Melanie Eggermont, Jolien Vandewalle, Lise Van Wyngene, Karolien De Bosscher, and Claude Libert. 2020. “Glucocorticoids Limit Lipopolysaccharide‐induced Lethal Inflammation by a Double Control System.” EMBO REPORTS.
Vancouver
1.
Van Looveren K, Timmermans S, Vanderhaeghen T, Wallaeys C, Ballegeer M, Souffriau J, et al. Glucocorticoids limit lipopolysaccharide‐induced lethal inflammation by a double control system. EMBO REPORTS. 2020;
IEEE
[1]
K. Van Looveren et al., “Glucocorticoids limit lipopolysaccharide‐induced lethal inflammation by a double control system,” EMBO REPORTS, 2020.
@article{8661631,
  abstract     = {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.},
  articleno    = {e49762},
  author       = {Van Looveren, Kelly and Timmermans, Steven and Vanderhaeghen, Tineke and Wallaeys, Charlotte and Ballegeer, Marlies and Souffriau, Jolien and Eggermont, Melanie and Vandewalle, Jolien and Van Wyngene, Lise and De Bosscher, Karolien and Libert, Claude},
  issn         = {1469-221X},
  journal      = {EMBO REPORTS},
  keywords     = {Genetics,Biochemistry,Molecular Biology},
  language     = {eng},
  pages        = {17},
  title        = {Glucocorticoids limit lipopolysaccharide‐induced lethal inflammation by a double control system},
  url          = {http://dx.doi.org/10.15252/embr.201949762},
  year         = {2020},
}

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