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.
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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 |
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