title: Enhancing nuclear translocation: perspectives in inhaled corticosteroid therapy.
abstract: Corticosteroids are widely used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). In contrast to their use in mild-to-moderate asthma, they are less efficacious in improving lung function and controlling the underlying inflammation in COPD. In most clinical trials, corticosteroids have shown little benefit in COPD, but have shown a greater clinical effect in combination with long-acting bronchodilators. Impaired corticosteroid activation of the glucocorticoid receptor (GR) has been reported in corticosteroid-insensitive individuals. Reversal of corticosteroid-insensitivity by enhancing GR nuclear translocation is a potential therapeutic target. Preclinical studies suggest members of the nuclear receptor superfamily may facilitate glucocorticoid receptor nuclear translocation. Unravelling the mechanisms that govern GR nuclear translocation may identify novel therapeutic targets for reversing corticosteroid-insensitivity.
authors.affiliation: National Heart & Lung Institute, Airway Disease Section, Imperial College London & Royal Brompton Hospital, Dovehouse Street, London, SW3 6LY UK.
authors.forename: Amir
authors.initials: A
authors.lastname: Hakim
authors.forename: Omar S
authors.initials: OS
authors.lastname: Usmani
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D004359:Drug Therapy, Combination; D006801:Humans; D008954:Models, Biological; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
chemical_list: D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D011965:Receptors, Glucocorticoid
keywords: glucocorticoid receptor; inhaled corticosteroids; nuclear translocation