scholarly journals Interaction of cytokine- and glucocorticoid-response elements of acute-phase plasma protein genes. Importance of glucocorticoid receptor level and cell type for regulation of the elements from rat alpha 1-acid glycoprotein and beta-fibrinogen genes.

1990 ◽  
Vol 265 (36) ◽  
pp. 22275-22281 ◽  
Author(s):  
H Baumann ◽  
G P Jahreis ◽  
K K Morella
Keyword(s):  
Glucocorticoid Receptor ◽  
Acute Phase ◽  
Plasma Protein ◽  
Cell Type ◽  
Response Elements ◽  
Receptor Level ◽  
Acid Glycoprotein ◽  
Glucocorticoid Response ◽  
Glucocorticoid Response Elements

scholarly journals The permissive role of glucocorticoids on interleukin-1 stimulation of angiotensinogen gene transcription is mediated by an interaction between inducible enhancers.

1990 ◽  
Vol 10 (8) ◽  
pp. 4389-4395 ◽  
Author(s):  
D Ron ◽  
A R Brasier ◽  
K A Wright ◽  
J F Habener
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Interleukin 1 ◽  
Luciferase Reporter ◽  
Nf Kappa B ◽  
Response Elements ◽  
Glucocorticoid Response ◽  
Glucocorticoid Response Elements ◽  
Permissive Role

The acute-phase activation of the rat angiotensinogen (rAT) gene in liver cells is a transcriptional event mediated through an interleukin-1-inducible, NF kappa B-binding, cis-acting element (the acute-phase response element [APRE]). Using a cell culture model for the acute-phase response, we showed that the increase in angiotensionogen mRNA in H35 rat hepatoma cells requires costimulation with glucocorticoids and cytokines. Stably transfected rAT promoter-luciferase reporter genes were also activated by cytokines only in the presence of glucocorticoids. This permissive role of glucocorticoids is dependent on the expression of functional glucocorticoid receptors, because in HepG2 cells naturally deficient in such receptors, rAT gene-luciferase reporter constructs responded to interleukin-1 only when cotransfected with an expression vector for the glucocorticoid receptor. Point mutations in the two rAT gene glucocorticoid response elements located adjacent to the APRE led to loss of interleukin-1 inducibility. Induction of luciferase activity in transfected cells occurred even in the presence of cycloheximide, demonstrating that this synergistic response did not depend on new protein synthesis. Thus, a direct interaction between the interleukin-1-inducible NF kappa B-binding APRE and glucocorticoid response elements, located in cis, underlies the acute-phase activation of the rAT gene.

The permissive role of glucocorticoids on interleukin-1 stimulation of angiotensinogen gene transcription is mediated by an interaction between inducible enhancers

1990 ◽  
Vol 10 (8) ◽  
pp. 4389-4395
Author(s):  
D Ron ◽  
A R Brasier ◽  
K A Wright ◽  
J F Habener
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Interleukin 1 ◽  
Luciferase Reporter ◽  
Nf Kappa B ◽  
Response Elements ◽  
Glucocorticoid Response ◽  
Glucocorticoid Response Elements ◽  
Permissive Role

The acute-phase activation of the rat angiotensinogen (rAT) gene in liver cells is a transcriptional event mediated through an interleukin-1-inducible, NF kappa B-binding, cis-acting element (the acute-phase response element [APRE]). Using a cell culture model for the acute-phase response, we showed that the increase in angiotensionogen mRNA in H35 rat hepatoma cells requires costimulation with glucocorticoids and cytokines. Stably transfected rAT promoter-luciferase reporter genes were also activated by cytokines only in the presence of glucocorticoids. This permissive role of glucocorticoids is dependent on the expression of functional glucocorticoid receptors, because in HepG2 cells naturally deficient in such receptors, rAT gene-luciferase reporter constructs responded to interleukin-1 only when cotransfected with an expression vector for the glucocorticoid receptor. Point mutations in the two rAT gene glucocorticoid response elements located adjacent to the APRE led to loss of interleukin-1 inducibility. Induction of luciferase activity in transfected cells occurred even in the presence of cycloheximide, demonstrating that this synergistic response did not depend on new protein synthesis. Thus, a direct interaction between the interleukin-1-inducible NF kappa B-binding APRE and glucocorticoid response elements, located in cis, underlies the acute-phase activation of the rAT gene.

Structural insights into glucocorticoid receptor function

2021 ◽  
Author(s):  
Filipp Frank ◽  
Eric A. Ortlund ◽  
Xu Liu
Keyword(s):  
Glucocorticoid Receptor ◽  
Inflammatory Responses ◽  
Therapeutic Index ◽  
Response Elements ◽  
Intrinsically Disordered ◽  
Current State ◽  
Glucocorticoid Response ◽  
Condensate Formation ◽  
Context Specific ◽  
Glucocorticoid Response Elements

The glucocorticoid receptor (GR) is a steroid hormone-activated transcription factor that binds to various glucocorticoid response elements to up- or down- regulate the transcription of thousands of genes involved in metabolism, development, stress and inflammatory responses. GR consists of two domains enabling interaction with glucocorticoids, DNA response elements and coregulators, as well as a large intrinsically disordered region that mediates condensate formation. A growing body of structural studies during the past decade have shed new light on GR interactions, providing a new understanding of the mechanisms driving context-specific GR activity. Here, we summarize the established and emerging mechanisms of action of GR, primarily from a structural perspective. This minireview also discusses how the current state of knowledge of GR function may guide future glucocorticoid design with an improved therapeutic index for different inflammatory disorders.

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