In primary acute lymphoblastic leukemia cells exhibiting de novo resistance to glucocorticoids, we recently discovered decreased promoter methylation of caspase 1 (CASP1) and NLR family, pyrin domain containing 3 (NLRP3), which resulted in increased transcription, constitutive NALP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome activation, and caspase 1-mediated cleavage of the glucocorticoid receptor. This revealed a novel mechanism of glucocorticoid resistance that was recapitulated in model systems.
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http://dx.doi.org/10.1080/23723556.2015.1065947 | DOI Listing |
JCEM Case Rep
February 2025
University of Utah Health, Division of Endocrinology, Salt Lake City, UT 84108, USA.
Glucocorticoid resistance syndrome (GRS) is caused by inactivating pathogenic variants in the glucocorticoid receptor gene . Reduced glucocorticoid receptor signaling leads to decreased tissue sensitivity to cortisol and resultant biochemical hypercortisolism without the classic clinical features of Cushing syndrome. Patients variably present with signs and symptoms of mineralocorticoid and androgen excess from ACTH overstimulation of the adrenal cortex.
View Article and Find Full Text PDFInflamm Res
January 2025
Institute of Otolaryngology head and neck surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Objective: This study seeks to elucidate the role and molecular mechanisms of IL-8 in nasal epithelial cell pyroptosis and its impact on glucocorticoid (GC) resistance.
Methods: We assessed the expression of pyroptosis-related biomarkers and IL-8 in tissues and human nasal epithelial cells (hNECs) from both control and nasal polyp patients using western blot. Their localization was determined through immunohistochemistry and immunofluorescence.
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.
Front Endocrinol (Lausanne)
November 2024
Section of Medicine, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
Front Med
December 2024
Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB).
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