Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.coph.2019.04.010
Title: Pharmacological strategies to regain steroid sensitivity in severe asthma and COPD
Authors: Mei, Dan
Tan, Wan Shun Daniel 
Wong, Wai Shiu Fred 
Keywords: Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
OBSTRUCTIVE PULMONARY-DISEASE
AIRWAY HYPERRESPONSIVENESS
CORTICOSTEROID SENSITIVITY
EPITHELIAL-CELLS
MOUSE MODELS
RESISTANCE
THEOPHYLLINE
EXPRESSION
EXACERBATIONS
INHIBITION
Issue Date: 1-Jun-2019
Publisher: ELSEVIER SCI LTD
Citation: Mei, Dan, Tan, Wan Shun Daniel, Wong, Wai Shiu Fred (2019-06-01). Pharmacological strategies to regain steroid sensitivity in severe asthma and COPD. CURRENT OPINION IN PHARMACOLOGY 46 : 73-81. ScholarBank@NUS Repository. https://doi.org/10.1016/j.coph.2019.04.010
Abstract: Corticosteroid is the most widely used anti-inflammatory agent for asthma and chronic obstructive pulmonary disease (COPD). However, most of the severe asthmatics and COPD patients show poor response to the anti-inflammatory benefits of corticosteroids. Corticosteroid resistance is a major therapeutic challenge to the treatment of severe asthma and COPD. Cellular and molecular mechanisms underlying steroid insensitivity in severe asthma and COPD are still not fully understood. This review aims to recapitulate recent discoveries of potential contributing mechanisms of steroid resistance, and to appraise new therapeutic strategies shown to restore steroid sensitivity in experimental models of severe asthma and COPD, and in human clinical trials. It has been revealed that pro-inflammatory cytokines such as IFN-γ, TNF-α, TGF-β, IL-17A, IL-27, IL-33 and thymic stromal lymphopoietin (TSLP)may contribute to steroid resistance in severe asthma and COPD. These cytokines together with allergens, pathogens, and cigarette smoke can modulate multiple signaling pathways including PI3Kδ/Akt/mTOR, JAK1/2-STAT1/5, p38MAPK/JNK, Nrf2/HDAC2/c-Jun, heightened glucocorticoid receptor (GR)β/GRα ratio, and casein kinase 1 (CK1δ/ε)/cofilin 1, to induce steroid insensitivity. More recently, microRNAs such as miR-9, miR-21, and miR-126 have been implicated for corticosteroid insensitivity in asthma and COPD. Therapeutic strategies such as cytokine-specific biologics, signaling molecule-specific small molecule inhibitors, and microRNA-specific antagomir oligonucleotides are potentially promising approaches to reverse corticosteroid resistance. A panel of clinically effective drugs have shown promise in restoring steroid resistance in experimental models, and it is highly probable that some of these molecules can be successfully repositioned for the clinical use in COPD and severe asthma.
Source Title: CURRENT OPINION IN PHARMACOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/229077
ISSN: 14714892
14714973
DOI: 10.1016/j.coph.2019.04.010
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
Steroid Resistance Curr Opin Pharmacol 2019.pdf669.89 kBAdobe PDF

CLOSED

None

SCOPUSTM   
Citations

23
checked on Sep 23, 2022

Page view(s)

24
checked on Sep 22, 2022

Download(s)

3
checked on Sep 22, 2022

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.