Overcoming Steroid Insensitivity in Respiratory Disease

Written by well-known experts in field, this is the first book dedicated to dealing with the single most challenging management issue in long-term steroid therapy.Overcoming Steroid Insensitivity in Respiratory Disease reviews important new advances in therapeutics and provides the clinician with the most up to date information on one of the most significant therapeutic challenges to effective management of these diseases. This unique book is an invaluable resource for all postgraduate students and specialist physicians in pulmonology allergy and asthma. It is also of interest for workers in biomedical and pharmaceutical research.

ContentsList of contributorsPreface1 Molecular Mechanisms of Glucocorticoid Receptor ActionPankaj Bhavsar and Ian M. Adcock1.1 Introduction1.2 Glucocorticoid receptor1.3 Gene induction by GR1.4 GR transactivation and histone acetylation1.5 Post-translational modifications of GR1.6 Repression of NF-êB-induced inflammatory gene expression by GR-NF-êB1.7 GR-NF-êB cross-talk1.8 Role of HDAC2 in glucocorticoid function1.9 Overexpression of HDAC2 restores glucocorticoid sensitivity in alveolar macrophages1.10 Acetylation of hsp90 and regulation of GR function1.11 Other mechanisms of GR action1.12 Conclusions2 Side Effects of Topical and Oral GlucocorticoidsHeike Sch+cke, Khusru Asadullah and Wolf-Dietrich D_cke2.1 Introduction2.2 Glucocorticoid-induced side effects2.3 Summary3 Glucocorticoid Receptor Subtypes and Steroid SensitivityRobert H. Oakley and John A. Cidlowski3.1 Introduction3.2 Overview of classic GR function3.3 GR subtypes arising from alternative splicing3.4 GR subtypes arising from alternative translation initiation3.5 Conclusions4 Dissociated GlucocorticoidsIan M. Adcock4.1 Introduction4.2 Asthma and chronic obstructive pulmonary disease are chronic inflammatory diseases of the airways4.3 Regulation of inflammatory gene expression4.4 Effects on inflammation4.5 Mechanisms of glucocorticoid action4.6 Dissociated glucocorticoids4.7 GR cross-talk with other nuclear receptors and coactivators4.8 Overcoming steroid insensitivity4.9 Glucorticoid-sparing approaches to anti-inflammatory therapy4.10 Conclusion5 Generalized Glucocorticoid Insensitivity: Clinical Phenotype and Molecular MechanismsEvangelia Charmandari, Tomoshige Kino and George P. Chrousos5.1 Introduction5.2 Molecular mechanisms of glucocorticoid resistance5.3 Conclusions6 Corticosteroid Responsiveness in Asthma: Clinical AspectsKian Fan Chung6.1 Introduction6.2 Effects of corticosteroids in asthma6.3 Definition of corticosteroid insensitivity6.4 Oral CS responsiveness in asthma6.5 ICS responsiveness in asthma6.6 CS responsiveness in severe asthma6.7 Surrogates for CS responsiveness in asthma6.8 Pharmacokinetics of systemic CS in severe asthma6.9 CS responsiveness in cigarette smokers and chronic obstructive pulmonary disease6.10 Other diseases of CS insensitivity6.11 Conclusions7 Glucocorticoid-insensitive Asthma: Molecular MechanismsJohn W. Bloom7.1 Introduction7.2 GR abnormalities7.3 GR nuclear translocation7.4 Cross-talk with transcription factors7.5 NF-kB, GR, histones and chromatin remodelling7.6 Epigenetics and asthma7.7 Conclusions8 Cigarette Smoke, Oxidative Stress and Corticosteroid ResponsivenessIrfan Rahman and David Adenuga8.1 Oxidative stress8.2 Cigarette smoke/oxidative stress-induced NF-kB-mediated pro-inflammatory gene expression8.3 Histone acetylation and deacetylation8.4 Corticosteroids8.5 Histone deacetylases8.6 Reversing Glucocorticoids / Corticosteroid resistance8.7 Conclusion9 Regulation of Glucocorticoid Sensitivity by Macrophage Migration Inhibitory FactorEric F. Morand9.1 Introduction9.2 MIF as a pro-inflammatory factor9.3 Relationship between MIF and glucocorticoids