Abstract
Endogenous glucocorticoids exert a diverse array of physiological processes including immunemodulatory or anti-inflammatory responses and play an important role in the pathogenesis of inflammatory and autoimmune diseases. Regulation of inflammatory processes by glucocorticoids is controlled in a cytokinehypothalamo- pituitary-adrenal axis feedback circuit and on the local, cell-type and context-specific local regulatory system. At the tissue level the sensitivity and response to glucocorticoids are determined by multiple factors: including the local availability to glucocorticoids transported by blood, the locally-formed bioactive glucocorticoids (synthesized and metabolized 11β-hydroxysteroid dehydrogenase enzymes), the number and function of the glucocorticoid receptor (GR) and the GR affinity to its ligands. Numerous molecular factors are known to influence the sensitivity of glucocorticoid response through the GR. Cytokines are one of the major components that can inhibit GR function and can potentiate the resistance against glucocorticoids. GR isoforms, generated by alternative splicing, alternative translation and posttranslation modification are further mechanisms which modulate glucocorticoid signaling. Genetic variants within the GR encoding gene are other potential factors that may influence the susceptibility and severity of autoimmune disorders and may play a key role in individual response to medication. In this review our aim was to summarize our knowledge about the connections between the cell type-specific glucocorticoid signaling and the local immune system. Prediction of individual sensitivity to steroids and identification of key players in development of glucocorticoid resistance are essential in individualized therapies. The local, tissue-specific glucocorticoid signaling and its influence by cytokines may be important in determining the magnitude of inflammatory reactions, and may also be related to the success of glucocorticoidcontaining therapeutic strategies.
Keywords: 11β-Hydroxysteroid dehydrogenase enzyme, autoimmune diseases, glucocorticoid receptor.
Current Medicinal Chemistry
Title:Tissue-specific Glucocorticoid Signaling May Determine the Resistance Against Glucocorticoids in Autoimmune Diseases
Volume: 22 Issue: 9
Author(s): A. Szappanos, Z. Nagy, B. Kovacs, G. Poor, M. Toth, K. Racz, E. Kiss and A. Patocs
Affiliation:
Keywords: 11β-Hydroxysteroid dehydrogenase enzyme, autoimmune diseases, glucocorticoid receptor.
Abstract: Endogenous glucocorticoids exert a diverse array of physiological processes including immunemodulatory or anti-inflammatory responses and play an important role in the pathogenesis of inflammatory and autoimmune diseases. Regulation of inflammatory processes by glucocorticoids is controlled in a cytokinehypothalamo- pituitary-adrenal axis feedback circuit and on the local, cell-type and context-specific local regulatory system. At the tissue level the sensitivity and response to glucocorticoids are determined by multiple factors: including the local availability to glucocorticoids transported by blood, the locally-formed bioactive glucocorticoids (synthesized and metabolized 11β-hydroxysteroid dehydrogenase enzymes), the number and function of the glucocorticoid receptor (GR) and the GR affinity to its ligands. Numerous molecular factors are known to influence the sensitivity of glucocorticoid response through the GR. Cytokines are one of the major components that can inhibit GR function and can potentiate the resistance against glucocorticoids. GR isoforms, generated by alternative splicing, alternative translation and posttranslation modification are further mechanisms which modulate glucocorticoid signaling. Genetic variants within the GR encoding gene are other potential factors that may influence the susceptibility and severity of autoimmune disorders and may play a key role in individual response to medication. In this review our aim was to summarize our knowledge about the connections between the cell type-specific glucocorticoid signaling and the local immune system. Prediction of individual sensitivity to steroids and identification of key players in development of glucocorticoid resistance are essential in individualized therapies. The local, tissue-specific glucocorticoid signaling and its influence by cytokines may be important in determining the magnitude of inflammatory reactions, and may also be related to the success of glucocorticoidcontaining therapeutic strategies.
Export Options
About this article
Cite this article as:
Szappanos A., Nagy Z., Kovacs B., Poor G., Toth M., Racz K., Kiss E. and Patocs A., Tissue-specific Glucocorticoid Signaling May Determine the Resistance Against Glucocorticoids in Autoimmune Diseases, Current Medicinal Chemistry 2015; 22 (9) . https://dx.doi.org/10.2174/0929867321666141216125012
DOI https://dx.doi.org/10.2174/0929867321666141216125012 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Regulatory T Cell Therapy for Type I Diabetes Targeting on β Cell Associated Autoantigens
Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued) Erythropoietin Directly Affects Human Macrophage Functionality
Current Pharmaceutical Biotechnology Emerging Role of Regulatory T Cells in Gene Transfer
Current Gene Therapy Cytokine Therapies in Crohns Disease: Where are We Now and where should We Go?
Inflammation & Allergy - Drug Targets (Discontinued) Recent Advances in the Development of Novel Therapeutics Targeting Dendritic Cells
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Review of Recent Clinical Developments and Patents for the Treatment of Autoimmune and Inflammatory Diseases by Mesenchymal Stromal Cells
Recent Patents on Regenerative Medicine Deciphering the Antibodyome - Peptide Arrays for Serum Antibody Biomarker Diagnostics
Current Proteomics The Roles of MicroRNAs in Atherosclerosis
Current Medicinal Chemistry Current and Future Therapies Targeting the Immune System in Multiple Sclerosis
Current Pharmaceutical Biotechnology Molecular Field Analysis (MFA) and Other QSAR Techniques in Development of Phosphatase Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Therapeutic Potential of Natural Products from Terrestrial Plants as TNF-α Antagonist
Current Topics in Medicinal Chemistry Synthetic Sphingosine 1-Phosphate Receptor Modulators - Opportunities and Potential Pitfalls
Current Topics in Medicinal Chemistry The Role of Infections in the Pathogenesis of Autoimmune Diseases
Current Drug Targets - Inflammation & Allergy T Cell-Activated Signaling Pathways and Locally Produced Cytokines as Potential Targets in Celiac Disease
Current Drug Targets The Role of HLA Promoters in Autoimmunity
Current Pharmaceutical Design Therapeutic Potential of Glycolipid Ligands for Natural Killer (NK) T Cells in the Suppression of Autoimmune Diseases
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Immunomodulatory Role of Arsenic in Regulatory T Cells
Endocrine, Metabolic & Immune Disorders - Drug Targets Oral Contraceptives and Autoimmune Diseases
Current Women`s Health Reviews Metformin one in a Million Efficient Medicines for Rheumatoid Arthritis Complications: Inflammation, Osteoblastogenesis, Cardiovascular Disease, Malignancies
Current Rheumatology Reviews Role of CD73 in Disease: Promising Prognostic Indicator and Therapeutic Target
Current Medicinal Chemistry