Publications by authors named "Jolien Vandewalle"

18 Publications

  • Page 1 of 1

Macrophage miR-210 induction and metabolic reprogramming in response to pathogen interaction boost life-threatening inflammation.

Sci Adv 2021 May 7;7(19). Epub 2021 May 7.

Laboratory of Tumor Inflammation and Angiogenesis, CCB, VIB, Leuven, Belgium.

Unbalanced immune responses to pathogens can be life-threatening although the underlying regulatory mechanisms remain unknown. Here, we show a hypoxia-inducible factor 1α-dependent microRNA (miR)-210 up-regulation in monocytes and macrophages upon pathogen interaction. MiR-210 knockout in the hematopoietic lineage or in monocytes/macrophages mitigated the symptoms of endotoxemia, bacteremia, sepsis, and parasitosis, limiting the cytokine storm, organ damage/dysfunction, pathogen spreading, and lethality. Similarly, pharmacologic miR-210 inhibition improved the survival of septic mice. Mechanistically, miR-210 induction in activated macrophages supported a switch toward a proinflammatory state by lessening mitochondria respiration in favor of glycolysis, partly achieved by downmodulating the iron-sulfur cluster assembly enzyme ISCU. In humans, augmented miR-210 levels in circulating monocytes correlated with the incidence of sepsis, while serum levels of monocyte/macrophage-derived miR-210 were associated with sepsis mortality. Together, our data identify miR-210 as a fine-tuning regulator of macrophage metabolism and inflammatory responses, suggesting miR-210-based therapeutic and diagnostic strategies.
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http://dx.doi.org/10.1126/sciadv.abf0466DOI Listing
May 2021

Zinc inhibits lethal inflammatory shock by preventing microbe-induced interferon signature in intestinal epithelium.

EMBO Mol Med 2020 10 11;12(10):e11917. Epub 2020 Sep 11.

Center for Inflammation Research, VIB, Ghent, Belgium.

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.
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http://dx.doi.org/10.15252/emmm.201911917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539219PMC
October 2020

Glucocorticoids in Sepsis: To Be or Not to Be.

Front Immunol 2020 21;11:1318. Epub 2020 Jul 21.

Center for Inflammation Research, VIB, Ghent, Belgium.

Sepsis is a highly lethal syndrome resulting from dysregulated immune and metabolic responses to infection, thereby compromising host homeostasis. Activation of the hypothalamic-pituitary-adrenal (HPA) axis and subsequently adrenocortical glucocorticoid (GC) production during sepsis are important regulatory processes to maintain homeostasis. Multiple preclinical studies have proven the pivotal role of endogenous GCs in tolerance against sepsis by counteracting several of the sepsis characteristics, such as excessive inflammation, vascular defects, and hypoglycemia. Sepsis is however often complicated by dysfunction of the HPA axis, resulting from critical-illness-related corticosteroid insufficiency (CIRCI) and GC resistance. Therefore, GCs have been tested as an adjunctive therapy in sepsis and septic shock in different randomized clinical trials (RCTs). Nonetheless, these studies produced conflicting results. Interestingly, adding vitamin C and thiamin to GC therapy enhances the effects of GCs, probably by reducing GC resistance, and this results in an impressive reduction in sepsis mortality as was shown in two recent preliminary retrospective before-after studies. Multiple RCTs are currently underway to validate this new combination therapy in sepsis.
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http://dx.doi.org/10.3389/fimmu.2020.01318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396579PMC
April 2021

Glucocorticoids limit lipopolysaccharide-induced lethal inflammation by a double control system.

EMBO Rep 2020 07 8;21(7):e49762. Epub 2020 May 8.

VIB Center for Inflammation Research, Ghent, Belgium.

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.
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http://dx.doi.org/10.15252/embr.201949762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332980PMC
July 2020

Taking the STING Out of Sepsis?

Cell Host Microbe 2020 04;27(4):491-493

Center for Inflammation Research, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. Electronic address:

In this issue of Cell Host & Microbe, Zhang et al. use a sepsis mouse model to show that macrophage-specific release of coagulation factor F3 depends on pathogen detection and responses mediated by TMEM173/STING. The therapeutic power of targeting TMEM173/STING-F3 is evident in mice, but will it penetrate the sepsis bedside?
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http://dx.doi.org/10.1016/j.chom.2020.03.016DOI Listing
April 2020

GILZ in sepsis: "Poor is the pupil who does not surpass his master".

Eur J Immunol 2020 04 13;50(4):490-493. Epub 2020 Mar 13.

Center for Inflammation Research, VIB, Ghent, Belgium.

With the legendary saying of Leonardo da Vinci in the title, we suggest that Glucocorticoid Induced Leucine Zipper (GILZ) may have more promising effects against polymicrobial sepsis, than glucocorticoids (GC). Indeed, the use of GCs in sepsis remains a matter of debate. The rationale for their use in sepsis is to modulate the exaggerated inflammatory response while maintaining innate immunity. However, GC resistance and side-effects limit their therapeutic value in sepsis. Hence, there is a growing interest in understanding the mechanisms by which GCs modulate immune responses upon infection. In this issue of the European Journal of Immunology, Ellouze et al. provide data demonstrating that deregulated expression of GILZ, a GC-induced protein, in monocytes/macrophages (M/M) recovered from septic shock patients may contribute to the pathogenesis. Furthermore, the authors demonstrate that GILZ overexpression in M/M improves outcome in septic animals by limiting systemic inflammation while increasing bacterial clearance. Overall, these data provide evidence that GCs may modulate immune responses via GILZ and that GILZ is a valuable alternative for GC therapy in sepsis.
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http://dx.doi.org/10.1002/eji.202048582DOI Listing
April 2020

Hypoxia-inducible factors in metabolic reprogramming during sepsis.

FEBS J 2020 04 3;287(8):1478-1495. Epub 2020 Feb 3.

Center for Inflammation Research, VIB, Ghent, Belgium.

Sepsis is a highly heterogeneous syndrome that is caused by an imbalanced host response to infection. Despite huge investments, sepsis remains a contemporary threat with significant burden on health systems. Vascular dysfunction and elevated oxygen consumption by highly metabolically active immune cells result in tissue hypoxia during inflammation. The transcription factor hypoxia-inducible factor-1a (HIF1α), and its family members, plays an important role in cellular metabolism and adaptation to cellular stress caused by hypoxia. In this review, we discuss the role of HIF in sepsis. We show possible mechanisms by which the inflammatory response activated during sepsis affects the HIF pathway. The activated HIF pathway in turn changes the metabolism of both innate and adaptive immune cells. As HIF expression in leukocytes of septic patients can be directly linked with mortality, we discuss multiple ways of interfering with the HIF signaling pathway.
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http://dx.doi.org/10.1111/febs.15222DOI Listing
April 2020

Hepatic PPARα function and lipid metabolic pathways are dysregulated in polymicrobial sepsis.

EMBO Mol Med 2020 02 9;12(2):e11319. Epub 2020 Jan 9.

Center for Inflammation Research, VIB, Ghent, Belgium.

Despite intensive research and constant medical progress, sepsis remains one of the most urgent unmet medical needs of today. Most studies have been focused on the inflammatory component of the disease; however, recent advances support the notion that sepsis is accompanied by extensive metabolic perturbations. During times of limited caloric intake and high energy needs, the liver acts as the central metabolic hub in which PPARα is crucial to coordinate the breakdown of fatty acids. The role of hepatic PPARα in liver dysfunction during sepsis has hardly been explored. We demonstrate that sepsis leads to a starvation response that is hindered by the rapid decline of hepatic PPARα levels, causing excess free fatty acids, leading to lipotoxicity, and glycerol. In addition, treatment of mice with the PPARα agonist pemafibrate protects against bacterial sepsis by improving hepatic PPARα function, reducing lipotoxicity and tissue damage. Since lipolysis is also increased in sepsis patients and pemafibrate protects after the onset of sepsis, these findings may point toward new therapeutic leads in sepsis.
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http://dx.doi.org/10.15252/emmm.201911319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005534PMC
February 2020

A Study of Cecal Ligation and Puncture-Induced Sepsis in Tissue-Specific Tumor Necrosis Factor Receptor 1-Deficient Mice.

Front Immunol 2019 8;10:2574. Epub 2019 Nov 8.

VIB Center for Inflammation Research, Ghent, Belgium.

Sepsis is a complex syndrome resulting from a dysregulated immune response to an infection. Due to the high prevalence, morbidity, and mortality, there is a lot of interest in understanding pathways that play a role in sepsis, with a focus on the immune system. Tumor necrosis factor (TNF) is a pleiotropic pro-inflammatory cytokine and a master regulator of the immune system but clinical trials with TNF blockers in sepsis have failed to demonstrate significant protection. Since TNF stimulates two different receptors, TNF receptor 1 (TNFR1) and TNFR2, pan-TNF inhibition might be suboptimal since both receptors have opposite functions in polymicrobial sepsis. Therefore, we hypothesized that TNF has a dual role in sepsis, namely a mediating and a protective role, and that protection might be obtained by TNFR1-specific inhibition. We here confirmed that TNFR1 mice are protected in the sterile endotoxemia model, whereas TNFR1 deficiency did not protect in the cecal ligation and puncture (CLP)-induced polymicrobial sepsis model. Since whole body TNFR1 blockage might be deleterious because of the antibacterial function of TNF/TNFR1 signaling, we focused on the potential devastating role of TNF/TNFR1 signaling in specific cell types. We were interested in the gut epithelium, the endothelium, and hepatocytes using conditional TNFR1 mice, as these cell types have been shown to play a role in sepsis. However, none of these conditional knockout mice showed improved survival in the CLP model. We conclude that cell-specific targeting of TNFR1 to these cell types has no therapeutic future in septic peritonitis.
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http://dx.doi.org/10.3389/fimmu.2019.02574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856143PMC
October 2020

TNF-α inhibits glucocorticoid receptor-induced gene expression by reshaping the GR nuclear cofactor profile.

Proc Natl Acad Sci U S A 2019 06 10;116(26):12942-12951. Epub 2019 Jun 10.

Mouse Genetics in Inflammation, VIB Center for Inflammation Research, 9052 Ghent, Belgium;

Glucocorticoid resistance (GCR) is defined as an unresponsiveness to the therapeutic effects, including the antiinflammatory ones of glucocorticoids (GCs) and their receptor, the glucocorticoid receptor (GR). It is a problem in the management of inflammatory diseases and can be congenital as well as acquired. The strong proinflammatory cytokine TNF-alpha (TNF) induces an acute form of GCR, not only in mice, but also in several cell lines: e.g., in the hepatoma cell line BWTG3, as evidenced by impaired Dexamethasone (Dex)-stimulated direct GR-dependent gene up- and down-regulation. We report that TNF has a significant and broad impact on this transcriptional performance of GR, but no impact on nuclear translocation, dimerization, or DNA binding capacity of GR. Proteome-wide proximity-mapping (BioID), however, revealed that the GR interactome was strongly modulated by TNF. One GR cofactor that interacted significantly less with the receptor under GCR conditions is p300. NFκB activation and p300 knockdown both reduced direct transcriptional output of GR whereas p300 overexpression and NFκB inhibition reverted TNF-induced GCR, which is in support of a cofactor reshuffle model. This hypothesis was supported by FRET studies. This mechanism of GCR opens avenues for therapeutic interventions in GCR diseases.
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http://dx.doi.org/10.1073/pnas.1821565116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600915PMC
June 2019

Overexpression of Gilz Protects Mice Against Lethal Septic Peritonitis.

Shock 2019 08;52(2):208-214

VIB Center for Inflammation Research, Ghent, Belgium.

Sepsis in humans and experimental animals is characterized by an acute inflammatory response. glucocorticoids (GCs) are widely used for the treatment of many inflammatory disorders, yet their effectiveness in sepsis is debatable. One of the major anti-inflammatory proteins induced by GCs is glucocorticoid-induced leucine zipper (GILZ, coded by the TSC22D3 gene). We found that TSC22D3 mRNA expression is downregulated in white blood cells of human sepsis patients. Interestingly, transgenic GILZ-overexpressing mice (GILZ-tg) showed better survival rates in the cecal ligation and puncture (CLP) model of mouse sepsis. To our surprise, GILZ had only mild anti-inflammatory effects in this model, as the systemic proinflammatory response was not significantly reduced in GILZ-tg mice compared with control mice. During CLP, we observed reduced bacterial counts in blood of GILZ-tg mice compared with control mice. We found increased expression of Tsc22d3 mRNA specifically in peritoneal exudate cells in the CLP model, as well as increased capacity for bacterial phagocytosis of CD45 GILZ-tg cells compared with CD45 GILZ-wt cells. Hence, we believe that the protective effects of GILZ in the CLP model can be linked to a more efficient phagocytosis.
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http://dx.doi.org/10.1097/SHK.0000000000001252DOI Listing
August 2019

Reprogramming of basic metabolic pathways in microbial sepsis: therapeutic targets at last?

EMBO Mol Med 2018 08;10(8)

Center for Inflammation Research, VIB, Ghent, Belgium

Sepsis is a highly lethal and urgent unmet medical need. It is the result of a complex interplay of several pathways, including inflammation, immune activation, hypoxia, and metabolic reprogramming. Specifically, the regulation and the impact of the latter have become better understood in which the highly catabolic status during sepsis and its similarity with starvation responses appear to be essential in the poor prognosis in sepsis. It seems logical that new interventions based on the recognition of new therapeutic targets in the key metabolic pathways should be developed and may have a good chance to penetrate to the bedside. In this review, we concentrate on the pathological changes in metabolism, observed during sepsis, and the presumed underlying mechanisms, with a focus on the level of the organism and the interplay between different organ systems.
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http://dx.doi.org/10.15252/emmm.201708712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079534PMC
August 2018

Using the inbred mouse strain SPRET/EiJ to provide novel insights in inflammation and infection research.

Mamm Genome 2018 08 9;29(7-8):585-592. Epub 2018 Jun 9.

VIB Center for Inflammation Research, Technologiepark 927, 9052, Ghent, Belgium.

Inbred mouse strains derived from the species Mus spretus have been very informative in the study of certain gene polymorphisms in inflammation and infection. Based on our interest in sepsis, we used SPRET/EiJ mice and mapped several critical loci that are linked to sensitivity to cytokine-induced inflammation and endotoxemia. These studies were based on prominent phenotypes that have never been observed in strains derived from Mus musculus and we mapped them at a resolution that enables us to draw conclusions on the mechanisms. Now that the genome of SPRET/EiJ has been sequenced, and other tools have become available, it is time to revisit this strain and emphasize its advantages and disadvantages as a research tool and a discovery platform.
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http://dx.doi.org/10.1007/s00335-018-9751-xDOI Listing
August 2018

Glucocorticoid receptor dimers control intestinal STAT1 and TNF-induced inflammation in mice.

J Clin Invest 2018 08 25;128(8):3265-3279. Epub 2018 Jun 25.

VIB Center for Inflammation Research, Ghent, Belgium.

TNF is an important mediator in numerous inflammatory diseases, e.g., in inflammatory bowel diseases (IBDs). In IBD, acute increases in TNF production can lead to disease flares. Glucocorticoids (GCs), which are steroids that bind and activate the glucocorticoid receptor (GR), are able to protect animals and humans against acute TNF-induced inflammatory symptoms. Mice with a poor transcriptional response of GR dimer-dependent target genes were studied in a model of TNF-induced lethal inflammation. In contrast to the GRWT/WT mice, these GRdim/dim mice displayed a substantial increase in TNF sensitivity and a lack of protection by the GC dexamethasone (DEX). Unchallenged GRdim/dim mice had a strong IFN-stimulated gene (ISG) signature, along with STAT1 upregulation and phosphorylation. This ISG signature was gut specific and, based on our studies with antibiotics, depended on the gut microbiota. GR dimers directly bound to short DNA sequences in the STAT1 promoter known as inverted repeat negative GRE (IR-nGRE) elements. Poor control of STAT1 in GRdim/dim mice led to failure to repress ISG genes, resulting in excessive necroptosis induction by TNF. Our findings support a critical interplay among gut microbiota, IFNs, necroptosis, and GR in both the basal response to acute inflammatory challenges and pharmacological intervention by GCs.
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http://dx.doi.org/10.1172/JCI96636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063488PMC
August 2018

Therapeutic Mechanisms of Glucocorticoids.

Trends Endocrinol Metab 2018 01 20;29(1):42-54. Epub 2017 Nov 20.

Center for Inflammation Research, Vlaams Instituut voor Biotechnologie (VIB), Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. Electronic address:

Glucocorticoids (GCs) have been used clinically for decades as potent anti-inflammatory and immunosuppressive agents. Nevertheless, their use is severely hampered by the risk of developing side effects and the occurrence of glucocorticoid resistance (GCR). Therefore, efforts to understand the complex mechanisms underlying GC function and GCR are ongoing. The goal is to generate new glucocorticoid receptor (GR) ligands that can dissociate anti-inflammatory from metabolic side effects and/or overcome GCR. In this review paper we discuss recent insights into GR-mediated actions in GCR and novel therapeutic strategies for acute and chronic inflammatory diseases.
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http://dx.doi.org/10.1016/j.tem.2017.10.010DOI Listing
January 2018

Simultaneous Inhibition of Tumor Necrosis Factor Receptor 1 and Matrix Metalloproteinase 8 Completely Protects Against Acute Inflammation and Sepsis.

Crit Care Med 2018 01;46(1):e67-e75

Center for Inflammation Research, VIB, Zwijnaarde, Belgium.

Objectives: Sepsis causes very high mortality and morbidity rates and remains one of the biggest medical challenges. This study investigates whether plasma levels of both matrix metalloproteinase 8 and tumor necrosis factor receptor 1 are associated with sepsis severity and also investigates the therapeutic applicability of simultaneous inhibition of the two molecules in sepsis.

Design: Observational human pilot study-prospective controlled animal study.

Setting: University hospital and research laboratory.

Subjects: Sepsis patients and C57BL/6 mice deficient for matrix metalloproteinase 8 and/or tumor necrosis factor receptor 1.

Intervention: Plasma and whole blood RNA were collected from 13 sepsis patients for 7 consecutive days and within 24 hours of admission to ICU. Matrix metalloproteinase 8 and tumor necrosis factor receptor 1 plasma and expression levels were determined in these patients. Mice deficient for both matrix metalloproteinase 8 and tumor necrosis factor receptor 1 were generated and subjected to endotoxemia and cecal ligation and puncture. Additionally, a bispecific Nanobody that simultaneously blocks matrix metalloproteinase 8 and tumor necrosis factor receptor 1 was created.

Measurements And Main Results: Plasma levels of matrix metalloproteinase 8 and tumor necrosis factor receptor 1 were positively correlated with the Sequential Organ Failure Assessment score (r, 0.51 and 0.58) and interleukin 6 levels (r, 0.59 and 0.52) in 13 sepsis patients. Combined elimination of tumor necrosis factor receptor 1 and matrix metalloproteinase 8 in double knockout mice resulted in superior survival in endotoxemia and CLP compared with single knockouts and wild-type mice. Cotreatment with our bispecific Nanobody in CLP resulted in improved survival rates (28% vs 19%) compared with untreated mice.

Conclusions: Inhibition of matrix metalloproteinase 8 and tumor necrosis factor receptor 1 might have therapeutic potential to treat sepsis and proof-of-principle was provided as therapeutics that inhibit both tumor necrosis factor receptor 1 and matrix metalloproteinase 8 are effective in CLP.
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http://dx.doi.org/10.1097/CCM.0000000000002813DOI Listing
January 2018

Glucocorticoid Receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor.

Sci Rep 2017 08 21;7(1):8941. Epub 2017 Aug 21.

Receptor Research Laboratories, Cytokine Receptor Lab, VIB, Center for Medical Biotechnology, Ghent, Belgium.

The transcriptional activity of the glucocorticoid receptor (GR) is co-determined by its ability to recruit a vast and varying number of cofactors. We here identify Striatin-3 (STRN3) as a novel interaction partner of GR that interferes with GR's ligand-dependent transactivation capacity. Remarkably, STRN3 selectively affects only GR-dependent transactivation and leaves GR-dependent transrepression mechanisms unhampered. We found that STRN3 down-regulates GR transactivation by an additional recruitment of the catalytic subunit of protein phosphatase 2A (PPP2CA) to GR. We hypothesize the existence of a functional trimeric complex in the nucleus, able to dephosphorylate GR at serine 211, a known marker for GR transactivation in a target gene-dependent manner. The presence of STRN3 appears an absolute prerequisite for PPP2CA to engage in a complex with GR. Herein, the C-terminal domain of GR is essential, reflecting ligand-dependency, yet other receptor parts are also needed to create additional contacts with STRN3.
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http://dx.doi.org/10.1038/s41598-017-09246-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567040PMC
August 2017

Glucocorticoid-induced microRNA-511 protects against TNF by down-regulating TNFR1.

EMBO Mol Med 2015 Aug;7(8):1004-17

VIB Inflammation Research Center, Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium

TNF is a central actor during inflammation and a well-recognized drug target for inflammatory diseases. We found that the mouse strain SPRET/Ei, known for extreme and dominant resistance against TNF-induced shock, displays weak expression of TNF receptor 1 protein (TNFR1) but normal mRNA expression, a trait genetically linked to the major TNFR1 coding gene Tnfrsf1a and to a locus harbouring the predicted TNFR1-regulating miR-511. This miRNA is a genuine TNFR1 regulator in cells. In mice, overexpression of miR-511 down-regulates TNFR1 and protects against TNF, while anti-miR-511 up-regulates TNFR1 and sensitizes for TNF, breaking the resistance of SPRET/Ei. We found that miR-511 inhibits endotoxemia and experimental hepatitis and that this miR is strongly induced by glucocorticoids and is a true TNFR1 modulator and thus an anti-inflammatory miR. Since minimal reductions of TNFR1 have considerable effects on TNF sensitivity, we believe that at least part of the anti-inflammatory effects of glucocorti-coids are mediated by induction of this miR, resulting in reduced TNFR1 expression.
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http://dx.doi.org/10.15252/emmm.201405010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551340PMC
August 2015