Functional proteomics for the characterization of impaired cellular responses to glucocorticoids in asthma

Konrad Pazdrak, Alexander Kurosky

    Research output: Chapter in Book/Report/Conference proceedingChapter

    3 Scopus citations

    Abstract

    In chronic airway inflammatory disorders, such as asthma, glucocorticoid (GC) insensitivity is a challenging clinical problem associated with life-threatening disease progression and the potential development of serious side effects. The mechanism of steroid resistance in asthma remains unclear and may be multifactorial. Excluding noncompliance with GC treatment, abnormal steroid pharmacokinetics, and rare genetic defects in the glucocorticoid receptor (GR), the majority of GC insensitivity in asthma can be attributed to secondary defects related to GR function. Airway inflammatory cells obtained from patients with GC-resistant asthma show a number of abnormalities in cell immune responses to GC, which suggests that there is a causative defect in GR signaling in GC-resistant cells that could be further elucidated by a functional and molecular proteomics approach. Since T cells, eosinophils, and monocytes play a major role in the pathogenesis of airway inflammation, most of the work published to date has focused on these cell types as the primary therapeutic targets in GC-insensitive asthma. We herein review several distinct techniques for the assessment of (1) the cellular response to GCs including the effect of GCs on cell viability, adhesion, and mediator release; (2) the functionality of GC receptors, including phosphorylation of the GR, nuclear translocation, and binding activities; and (3) the characterization of proteins differentially expressed in steroidresistant cells by comparative 2DE-gel electrophoresis-based techniques and mass spectrometry. These comprehensive approaches are expected to reveal novel candidates for biomarkers of steroid insensitivity, which may lead to the development of effective therapeutic interventions for patients with chronic steroid-resistant asthma.

    Original languageEnglish (US)
    Title of host publicationAdvances in Experimental Medicine and Biology
    PublisherSpringer New York LLC
    Pages255-270
    Number of pages16
    Volume795
    ISBN (Print)9781461486022
    DOIs
    StatePublished - 2014

    Publication series

    NameAdvances in Experimental Medicine and Biology
    Volume795
    ISSN (Print)00652598

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    Keywords

    • Airway inflammatory cells
    • Asthma
    • Biomarkers
    • Cell signaling pathways
    • Eosinophils
    • Glucocorticoids
    • Mass spectrometry
    • Phosphoproteomics
    • Proteomics
    • Steroid resistance

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Medicine(all)

    Cite this

    Pazdrak, K., & Kurosky, A. (2014). Functional proteomics for the characterization of impaired cellular responses to glucocorticoids in asthma. In Advances in Experimental Medicine and Biology (Vol. 795, pp. 255-270). (Advances in Experimental Medicine and Biology; Vol. 795). Springer New York LLC. https://doi.org/10.1007/978-1-4614-8603-9_16