Abstract
Asthma shows heterogeneity in the cellular sources of inflammation and response to therapy. Although glucocorticoids (GC) are very effective for the treatment of most patients with asthma, an important subgroup of patients fails to show clinical improvement. GC resistance (GC-R) could result from either inherited or acquired variation in GC sensitivity. Diverse cells, such as T helper (Th)1 cells, Th2 cells, and Th17 cells, and innate immunity associated pathways are involved in GC-R asthma. The GC receptor (GR) plays a central role in GC sensitivity. Recent molecular biological studies have revealed the involvement of protein kinase signaling to GR, GR phosphorylation, interactions of GR with excessive activation of transcription factors, and impaired histone deacetylase (HDAC). Long-acting β(2)-adrenoceptor agonists (LABAs) may improve the clinical efficacy of GCs by enhancing GR function. Inhibitors of kinase pathways, such as p38 mitogen-activated protein kinase (MAPK) inhibitors and phosphoinositide-3-kinase (PI3K)δ inhibitors, are candidates for new therapeutic agents for GC-R asthma.
Keywords: Glucocorticoid (GC), glucocorticoid-resistant (GC-R) asthma, glucocorticoid receptor (GR), histone deacetylase (HDAC), long-acting β(2)-adrenoceptor agonists (LABAs), mitogen-activated protein kinase (MAPK), phosphoinositide-3- kinase (PI3K).
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Title:Inflammatory Cellular Phenotypes and Molecular Mechanisms of Glucocorticoid Resistance in Patients with Bronchial Asthma
Volume: 12 Issue: 3
Author(s): Yasuhiro Matsumura
Affiliation:
Keywords: Glucocorticoid (GC), glucocorticoid-resistant (GC-R) asthma, glucocorticoid receptor (GR), histone deacetylase (HDAC), long-acting β(2)-adrenoceptor agonists (LABAs), mitogen-activated protein kinase (MAPK), phosphoinositide-3- kinase (PI3K).
Abstract: Asthma shows heterogeneity in the cellular sources of inflammation and response to therapy. Although glucocorticoids (GC) are very effective for the treatment of most patients with asthma, an important subgroup of patients fails to show clinical improvement. GC resistance (GC-R) could result from either inherited or acquired variation in GC sensitivity. Diverse cells, such as T helper (Th)1 cells, Th2 cells, and Th17 cells, and innate immunity associated pathways are involved in GC-R asthma. The GC receptor (GR) plays a central role in GC sensitivity. Recent molecular biological studies have revealed the involvement of protein kinase signaling to GR, GR phosphorylation, interactions of GR with excessive activation of transcription factors, and impaired histone deacetylase (HDAC). Long-acting β(2)-adrenoceptor agonists (LABAs) may improve the clinical efficacy of GCs by enhancing GR function. Inhibitors of kinase pathways, such as p38 mitogen-activated protein kinase (MAPK) inhibitors and phosphoinositide-3-kinase (PI3K)δ inhibitors, are candidates for new therapeutic agents for GC-R asthma.
Export Options
About this article
Cite this article as:
Matsumura Yasuhiro, Inflammatory Cellular Phenotypes and Molecular Mechanisms of Glucocorticoid Resistance in Patients with Bronchial Asthma, Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 2013; 12 (3) . https://dx.doi.org/10.2174/18715230113129990010
DOI https://dx.doi.org/10.2174/18715230113129990010 |
Print ISSN 1871-5230 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-614X |
- 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
Related Articles
-
1,2,3-Triazine Scaffold as a Potent Biologically Active Moiety: A Mini Review
Mini-Reviews in Medicinal Chemistry Phenanthroindolizidines and Phenanthroquinolizidines: Promising Alkaloids for Anti-Cancer Therapy
Current Bioactive Compounds Efficacy and Safety of Inhaled and Intranasal Corticosteroids
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Machine Learning in Discovery of New Antivirals and Optimization of Viral Infections Therapy
Current Medicinal Chemistry Delivery of Dry Powders to the Lungs: Influence of Particle Attributes from a Biological and Technological Point of View
Current Drug Delivery Review of Medicinal Plants Common to Traditional Chinese and Indian Medicines with Relevance to Non-Communicable Diseases
Current Traditional Medicine Can We Delay the Accelerated Lung Aging in COPD? Anti-Aging Molecules and Interventions
Current Drug Targets Neuroprotective Strategies for Neurological Disorders by Natural Products: An update
Current Neuropharmacology Protocatechuic Acid Alkyl Esters: Hydrophobicity As a Determinant Factor for Inhibition of NADPH Oxidase
Current Medicinal Chemistry Cough Recording Technology
Current Respiratory Medicine Reviews Editorial (Thematic Issue: Immunophilins, Protein Chemistry and Cell Biology of a Promising New Class of Drug Targets – Part II)
Current Molecular Pharmacology New Strategies and Biological Agents in the Treatment of Autoimmune Inflammatory Diseases. Progress and Challenges
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Mast Cells in Lung Homeostasis: Beyond Type I Hypersensitivity
Current Respiratory Medicine Reviews Sao Paulo Research Conference on Molecular Medicine and Pharmacogenetics, A Joint Meeting with the IUPHAR Sub-Committee on Pharmacogenetics and the Brazilian Pharmacogenetics Network, Sao Paulo, Brazil, September 18-20, 2008
Current Pharmacogenomics and Personalized Medicine Inhalation Cough Challenge
Current Respiratory Medicine Reviews Raman Spectroscopy-based Metabonomics of HIV-infected Sera Detects Amino Acid and Glutathione Changes
Current Metabolomics Knowledge, Attitude, and Behavior in Avoiding Environmental Tobacco Smoke Exposure at Home among Pregnant Women
Current Women`s Health Reviews A Systematic Review of Meta-Analyses on Gene Polymorphisms and Gastric Cancer Risk
Current Genomics The Anti-inflammatory Potential of Selected Plant-derived Compounds in Respiratory Diseases
Current Pharmaceutical Design Nano-Therapeutics for the Lung: State-of-the-Art and Future Perspectives
Current Pharmaceutical Design