The differential expression of corticosteroid receptor isoforms in corticosteroid-resistant and -sensitive patients with rheumatoid arthritis

Abstract

We show for the first time that CRbeta is over-expressed in SR RA patients and that hydrocortisone fails to inhibit concanavalin-A stimulated increase in CRbeta mRNA in SR RA patients. This mechanism may contribute in part to the CS hyporesponsiveness seen in some RA patients.

The Clinical Role of Glucocorticoids in the Management of Rheumatoid Arthritis

“…IL-10 has been shown to enhance expression of GCR- (Xystrakis, 2005), which augments GC-responses (Lewis-Tuffin, 2006), and IL-17 upregulates the level of GCR- (Vazquez-Tello et al, 2010), which attenuates GC-responses. Consistent with this, PBMCs from GC-resistant patients with RA express higher levels of GCR- (Kozaci et al, 2007) as do bronchoalveolar lavage washings from patients with GCresistant asthma (Vazquez-Tello et al, 2010). As mentioned earlier, monocyte derived macrophages and dendritic cells have a huge influence on T helper phenotype differentiation and their precise role in this model requires further research.…”

“…GCR-is an alternatively spliced form of the GC receptor and its over-expression has been linked with GC resistance in asthma, RA and inflammatory bowel disease (Hamid et al, 1999;Sousa et al, 2000;Kozaci et al, 2007;Orii et al, 2002). GCR-does not bind GC and in fact its natural ligand (if it has one) remains unknown (Lewis-Tuffin, 2006).…”

Leukocyte-derived matrix metalloproteinase-9 in patients with coronary artery disease : Associations with psychological stress and glucocorticoid sensitivity

“…An increase in GR-β mRNA expression or a lowered GR-α/GR-β mRNA ratio has been associated with a state of glucocorticoid resistance in various cell lines (88,185). Similarly, increased expression of GR-β mRNA and protein in PBMCs has been reported in patients with glucocorticoid-resistant diseases such as asthma, rheumatoid arthritis and inflammatory bowel disease (89)(90)(91)(92). However, the proposed importance of GR-β-mediated repressive effects on GR-α has been questioned.…”

“…The upregulation of GR-β in human cell lines by IL-1 and TNF correlates with reduced GC sensitivity (88). In chronic inflammatory diseases such as rheumatoid arthritis, asthma and inflammatory bowel disease, increased gene expression of GR-β or lower ratio of GR-α/GR-β has been associated with GC unresponsiveness in vivo (89)(90)(91)(92). However, the latter is still a matter of debate since other clinical studies have not been able to detect any differences in GR-β expression (93)(94)(95).…”

Evaluation of Glucocorticoid Sensitivity and Its Potential Clinical Applicability

“…Interestingly, patients with GC-dependent disorders are those usually presenting tissue-specific resistance, such as in arthritis and asthma [4,5]. Concomitance of inadequate inflammatory control and excessive effects on the pituitary, bone and other tissues are common findings in these individuals, suggesting variability in cortisol metabolism and action in different tissues [6,7].…”