p300 plays a crucial role in the pathogenesis of HSPN. p300 can down-regulate the expression of resistance genes (AP-1 and TGF-β1) by binding with GRα to prevent further renal injury and glucocorticoid resistance.
No significant difference in expression levels of GR was found between groups POCD and non-POCD patients.High expression of FKBP51 in leukocytes and glucocorticoid resistance were associated with POCD in aged patients following hip fracture surgery.
Impaired GRα nuclear translocation and inhibited p-p65 expression might contribute to glucocorticoid resistance caused by MUC1 deficiency in TNF-α-induced necroptosis in 16HBE cells, and should be considered as a potential target for the development of novel therapeutics for asthma.
Therefore, the analyzed mutations compromise the GR ligand binding domain structure and cortisol binding, which could characterize the glucocorticoid resistance phenotype.
Combining our analyses of studies that reported DST results with those that used <i>in vitro</i> assays of GR function or <i>GR</i> expression to quantify glucocorticoid resistance (302 patients and 277 controls), we noted that although depressed patients produced more cytokines than controls (<i>d</i> = 1.02; 95% CI, 0.55-1.49), there was no evident positive correlation between glucocorticoid resistance and inflammation.
Glucocorticoid resistance syndrome (GRS) is caused by mutations of the glucocorticoid receptor (coded by the NR3C1 gene) and presents with signs of mineralocorticoid and/or androgen excess.
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.
Glucocorticoid resistance syndrome (GRS) is a rare genetic disorder caused by inactivating mutations of the NR3C1 gene which encodes the glucocorticoid receptor.
Several genetic defects, including point mutations, deletions or insertions in the NR3C1 gene that encodes the GR, have been associated with familial or sporadic generalized glucocorticoid resistance or Chrousos syndrome.
An unexpected, mild phenotype of glucocorticoid resistance associated with glucocorticoid receptor gene mutation case report and review of the literature.
Interestingly, these 3 pain states were associated with changes in glucocorticoid signalling, as indicated by the increased expression, at spinal cord level, of the glucocorticoid receptor isoform associated with glucocorticoid resistance, GRβ, and increased levels of plasma corticosterone.
In this review paper we discuss recent insights into GR-mediated actions in GCR and novel therapeutic strategies for acute and chronic inflammatory diseases.
Among these individuals, peritraumatic circulating <i>FKBP5</i> expression levels increased as cortisol and glucocorticoid receptor (<i>NR3C1</i>) mRNA levels increased, consistent with increased glucocorticoid resistance.
Our results suggest that specific inhibition of the AKT1/14-3-3 activity on the cytoplasmic retention of GR may be a promising target for treating glucocorticoid resistance observed in ALL.
Glucocorticoid resistance (GCR), i.e. unresponsiveness to the beneficial anti-inflammatory activities of the glucocorticoid receptor (GR), poses a serious problem in the treatment of inflammatory diseases.
A novel case of Chrousos syndrome has been reported in a patient with adrenal incidentaloma, who harboured a heterozygous point mutation in the hGR gene, which resulted in threonine (T) to isoleucine (I) substitution at amino acid position 556 in the ligand-binding domain of the receptor.
While these results prove that glucocorticoid receptor defects are crucial for glucocorticoid resistance in an experimental setting, they do not address the essential clinical situation where glucocorticoid resistance at relapse is rather part of a global drug resistance.
Chrousos syndrome is a rare pathologic condition characterized by generalized, partial resistance of target tissues to glucocorticoids and caused by inactivating mutations of the human glucocorticoid receptor (hGR) gene.