Association of Glucocorticoid Insensitivity with Increased Expression of Glucocorticoid Receptor β

DOI PDF 被引用文献13件
  • Donald Y.M. Leung
    From the *Divisions of Allergy-Immunology and Clinical Pharmacology, National Jewish Medical and Research Center, and the ‡Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado; the §Meakins-Christie Laboratories and Departments of Pathology, McGill University, Montreal, Quebec, Canada; and the §Developmental Endocrinology Branch, National Institutes of Health, Bethesda, Maryland
  • Qutayba Hamid
    From the *Divisions of Allergy-Immunology and Clinical Pharmacology, National Jewish Medical and Research Center, and the ‡Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado; the §Meakins-Christie Laboratories and Departments of Pathology, McGill University, Montreal, Quebec, Canada; and the §Developmental Endocrinology Branch, National Institutes of Health, Bethesda, Maryland
  • Alessandra Vottero
    From the *Divisions of Allergy-Immunology and Clinical Pharmacology, National Jewish Medical and Research Center, and the ‡Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado; the §Meakins-Christie Laboratories and Departments of Pathology, McGill University, Montreal, Quebec, Canada; and the §Developmental Endocrinology Branch, National Institutes of Health, Bethesda, Maryland
  • Stanley J. Szefler
    From the *Divisions of Allergy-Immunology and Clinical Pharmacology, National Jewish Medical and Research Center, and the ‡Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado; the §Meakins-Christie Laboratories and Departments of Pathology, McGill University, Montreal, Quebec, Canada; and the §Developmental Endocrinology Branch, National Institutes of Health, Bethesda, Maryland
  • Wendy Surs
    From the *Divisions of Allergy-Immunology and Clinical Pharmacology, National Jewish Medical and Research Center, and the ‡Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado; the §Meakins-Christie Laboratories and Departments of Pathology, McGill University, Montreal, Quebec, Canada; and the §Developmental Endocrinology Branch, National Institutes of Health, Bethesda, Maryland
  • Eleanor Minshall
    From the *Divisions of Allergy-Immunology and Clinical Pharmacology, National Jewish Medical and Research Center, and the ‡Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado; the §Meakins-Christie Laboratories and Departments of Pathology, McGill University, Montreal, Quebec, Canada; and the §Developmental Endocrinology Branch, National Institutes of Health, Bethesda, Maryland
  • George P. Chrousos
    From the *Divisions of Allergy-Immunology and Clinical Pharmacology, National Jewish Medical and Research Center, and the ‡Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado; the §Meakins-Christie Laboratories and Departments of Pathology, McGill University, Montreal, Quebec, Canada; and the §Developmental Endocrinology Branch, National Institutes of Health, Bethesda, Maryland
  • Dwight J. Klemm
    From the *Divisions of Allergy-Immunology and Clinical Pharmacology, National Jewish Medical and Research Center, and the ‡Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado; the §Meakins-Christie Laboratories and Departments of Pathology, McGill University, Montreal, Quebec, Canada; and the §Developmental Endocrinology Branch, National Institutes of Health, Bethesda, Maryland

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<jats:p>In many chronic inflammatory disorders, glucocorticoid (GC) insensitivity is a challenging clinical problem associated with life-threatening disease progression. The molecular basis of GC insensitivity, however, is unknown. Alternative splicing of the GC receptor (R) pre–messenger RNA generates a second GCR, termed GCR-β, which does not bind GCs but antagonizes the transactivating activity of the classic GCR, termed GCR-α. In the current study, we demonstrate that GC-insensitive asthma is associated with a significantly higher number of GCR-β–immunoreactive cells in peripheral blood than GC-sensitive asthmatics or normal controls. Furthermore, we show that patients with GC-insensitive asthma have cytokine-induced abnormalities in the DNA binding capability of the GCR. These abnormalities can be reproduced by transfection of cell lines with the GCR-β gene resulting in significant reduction of their GCR-α DNA binding capacity. We conclude that increased expression of GCR-β is cytokine inducible and may account for GC insensitivity in this common inflammatory condition.</jats:p>

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