Aim: Glucocorticoid (GC) resistant ulcerative colitis (UC) remains a serious disease and is difficult to manage. Although the molecular basis of GC insensitivity is still unknown, GC receptors (GRalpha and GRbeta) may play an important role in it. This study was aimed to investigate the relationship between the expression of GRalpha and GRbeta in colonic mucosal cells of patients with UC, the efficacy of GC therapy and the intensity of inflammation.
Methods: Twenty-five cases of UC were classified into: GC sensitive (n = 16) and GC resistant (n = 9) cases. Patients consisted of mild (n = 6), moderate (n = 8) and severe (n = 11) cases. GRalpha and GRbeta expression in colonic mucosal specimens were investigated by immunohistochemistry, and compared between GC resistant and sensitive groups, and also among various degrees of inflammation.
Results: All cases were positive for GRalpha and GRbeta expression. Both positive association between GRalpha expression and the response of UC to GC and strong negative association between GRbeta expression and the response of UC to GC were identified. There was no significant association between GRalpha/GRbeta expression and the degree of inflammation of UC.
Conclusion: These findings suggest that both GRalpha and GRbeta may play an important role in the action of GC, and that GRbeta functions as a dominant negative inhibitor of GRalpha. Expression of GRalpha and GRbeta in colonic mucosal cells of patients with UC may serve as predictors of glucocorticoid response, but can not function as markers of inflammatory intensity.
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http://dx.doi.org/10.3748/wjg.v11.i12.1775 | DOI Listing |
Arch Oral Biol
December 2024
Schulich Dentistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada. Electronic address:
Objective: We assessed levels of mRNA encoding two glucocorticoid receptor (GR) isoforms (GRα and GRβ) in saliva and examined their relationship with hair cortisol levels and dental caries experience.
Design: Adolescents and young adults were assessed for dental caries experience, and hair cortisol was measured by ELISA. RNA was extracted from whole saliva using TRIzol, followed by quantitative real-time PCR analysis of GRα, GRβ, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH).
Eur Arch Otorhinolaryngol
December 2024
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China.
Purpose: The objective of this study was to elucidate the relationship between adenoid hypertrophy (AH) and glucocorticoid resistance, and to investigate the potential reasons for the suboptimal therapeutic response to intranasal glucocorticoids (INS) in pediatric patients with AH.
Methods: The present study enrolled a cohort of 110 patients diagnosed with AH, all of whom underwent adenoidectomy at Renmin Hospital of Wuhan University between June 2023 and September 2023. Immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR) were employed to assess the levels of inflammatory cytokines, and glucocorticoid receptors (GR, including GRα and GRβ) in adenoidal tissues.
Adv Biol (Weinh)
November 2024
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
DNA damage underlies the progression of asthma toward a severe, steroid hyporesponsive phenotype. The accumulation of double-stranded DNA within the cytosol triggers the activation of cytosolic DNA-sensing pathways, notably the Stimulator of Interferon Genes (STING) pathway. However, the precise role of STING in driving steroid hyporesponsiveness remains elusive and warrants further investigation.
View Article and Find Full Text PDFProstaglandins Other Lipid Mediat
August 2024
Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA; Drug & Disease Discovery D3 Research Center, University of Kentucky College of Medicine, Lexington, KY, USA; Markey Cancer Center, University of Kentucky, Lexington, KY, USA; Barnstable Brown Diabetes Center, University of Kentucky, Lexington, KY, USA. Electronic address:
We have previously demonstrated that the glucocorticoid receptor β (GRβ) isoform induces hepatic steatosis in mice fed a normal chow diet. The GRβ isoform inhibits the glucocorticoid-binding isoform GRα, reducing responsiveness and inducing glucocorticoid resistance. We hypothesized that GRβ regulates lipids that cause metabolic dysfunction.
View Article and Find Full Text PDFRespir Res
May 2024
Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.
Background: Steroid insensitivity in Chronic Obstructive Pulmonary Disease (COPD) presents a problem for controlling the chronic inflammation of the airways. The glucocorticoid receptor (GR) mediates the intracellular signaling of inhaled corticosteroids (ICS) by interacting with transcription factors and histone deacetylases (HDACs). The aim of this study was to assess if COPD patients' response to ICS in vivo, may be associated with the expression of GR, the complex of GR with transcription factors, and the expression of various HDACs in vitro.
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