Inflammatory Cellular Phenotypes and Molecular Mechanisms of Glucocorticoid Resistance in Patients with Bronchial Asthma
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-
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