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Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages

(2012) FASEB JOURNAL. 26(2). p.722-729
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Abstract
Sepsis is controlled by endogenous glucocorticoids (GCs). Previous studies provided evidence that crosstalk of the monomeric GC receptor (GR) with proinflammatory transcription factors is the crucial mechanism underlying the suppressive GC effect. Here we demonstrate that mice with a dimerization-deficient GR (GR(dim)) are highly susceptible to sepsis in 2 different models, namely cecal ligation and puncture and lipopolysaccharide (LPS)-induced septic shock. TNF-alpha is normally regulated in these mice, but down-regulation of IL-6 and IL-1 beta is diminished. LPS-treated macrophages derived from GR(dim) mice are largely resistant to GC actions in vitro in terms of morphology, surface marker expression, and gene expression. Treatment with recombinant IL-1 receptor antagonist improved survival of GR(dim) mice and mice lacking the GR in macrophages (GR(LysMCre)) mice. This suggests that regulation of IL-1 beta in macrophages by GCs is pivotal to control sepsis.
Keywords
ACTIVATION, KAPPA-B, REPRESSION, MICE, PHOSPHATASE-1, DEXAMETHASONE, MAP KINASE, INFLAMMATORY RESPONSES, DNA-BINDING, CLP, GR, GENE-EXPRESSION, IL-1 beta

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Citation

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Chicago
Kleiman, Anna, Sabine Hübner, Jan M Rodriguez Parkitna, Anita Neumann, Stefan Hofer, Markus A Weigand, Michael Bauer, et al. 2012. “Glucocorticoid Receptor Dimerization Is Required for Survival in Septic Shock via Suppression of Interleukin-1 in Macrophages.” Faseb Journal 26 (2): 722–729.
APA
Kleiman, A., Hübner, S., Rodriguez Parkitna, J. M., Neumann, A., Hofer, S., Weigand, M. A., Bauer, M., et al. (2012). Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages. FASEB JOURNAL, 26(2), 722–729.
Vancouver
1.
Kleiman A, Hübner S, Rodriguez Parkitna JM, Neumann A, Hofer S, Weigand MA, et al. Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages. FASEB JOURNAL. 2012;26(2):722–9.
MLA
Kleiman, Anna, Sabine Hübner, Jan M Rodriguez Parkitna, et al. “Glucocorticoid Receptor Dimerization Is Required for Survival in Septic Shock via Suppression of Interleukin-1 in Macrophages.” FASEB JOURNAL 26.2 (2012): 722–729. Print.
@article{2067224,
  abstract     = {Sepsis is controlled by endogenous glucocorticoids (GCs). Previous studies provided evidence that crosstalk of the monomeric GC receptor (GR) with proinflammatory transcription factors is the crucial mechanism underlying the suppressive GC effect. Here we demonstrate that mice with a dimerization-deficient GR (GR(dim)) are highly susceptible to sepsis in 2 different models, namely cecal ligation and puncture and lipopolysaccharide (LPS)-induced septic shock. TNF-alpha is normally regulated in these mice, but down-regulation of IL-6 and IL-1 beta is diminished. LPS-treated macrophages derived from GR(dim) mice are largely resistant to GC actions in vitro in terms of morphology, surface marker expression, and gene expression. Treatment with recombinant IL-1 receptor antagonist improved survival of GR(dim) mice and mice lacking the GR in macrophages (GR(LysMCre)) mice. This suggests that regulation of IL-1 beta in macrophages by GCs is pivotal to control sepsis.},
  author       = {Kleiman, Anna and H{\"u}bner, Sabine and Rodriguez Parkitna, Jan M and Neumann, Anita and Hofer, Stefan and Weigand, Markus A and Bauer, Michael and Schmid, Wolfgang and Sch{\"u}tz, G{\"u}nter and Libert, Claude and Reichardt, Holger M and Tuckermann, Jan P},
  issn         = {0892-6638},
  journal      = {FASEB JOURNAL},
  keyword      = {ACTIVATION,KAPPA-B,REPRESSION,MICE,PHOSPHATASE-1,DEXAMETHASONE,MAP KINASE,INFLAMMATORY RESPONSES,DNA-BINDING,CLP,GR,GENE-EXPRESSION,IL-1 beta},
  language     = {eng},
  number       = {2},
  pages        = {722--729},
  title        = {Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages},
  url          = {http://dx.doi.org/10.1096/fj.11-192112},
  volume       = {26},
  year         = {2012},
}

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