title: Abnormal corticosteroid signalling in airway smooth muscle: mechanisms and perspectives for the treatment of severe asthma.
abstract: Growing in vivo evidence supports the concept that airway smooth muscle produces various immunomodulatory factors that could contribute to asthma pathogenesis via the regulation of airway inflammation, airway narrowing and remodelling. Targeting ASM using bronchial thermoplasty has provided undeniable clinical benefits for patients with uncontrolled severe asthma who are refractory to glucocorticoid therapy. The present review will explain why the failure of glucocorticoids to adequately manage patients with severe asthma could derive from their inability to affect the immunomodulatory potential of ASM. We will support the view that ASM sensitivity to glucocorticoid therapy can be blunted in severe asthma and will describe some of the factors and mechanisms that could be responsible for glucocorticoid insensitivity.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: L
authors.initials: L
authors.lastname: Chachi
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: A
authors.initials: A
authors.lastname: Gavrila
authors.affiliation: Department of Pharmaceutical Sciences, Thomas Jefferson University, Jefferson School of Pharmacy, Philadelphia, PA, USA.
authors.forename: O
authors.initials: O
authors.lastname: Tliba
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Amrani
mesh_terms: D000305:Adrenal Cortex Hormones / Q000378:metabolism* / Q000627:therapeutic use; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004351:Drug Resistance; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism; D056747:Immunomodulation; D009130:Muscle, Smooth / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000305:Adrenal Cortex Hormones; D016207:Cytokines; D007155:Immunologic Factors