Please use this identifier to cite or link to this item:
https://doi.org/10.1016/j.coph.2019.04.010
DC Field | Value | |
---|---|---|
dc.title | Pharmacological strategies to regain steroid sensitivity in severe asthma and COPD | |
dc.contributor.author | Mei, Dan | |
dc.contributor.author | Tan, Wan Shun Daniel | |
dc.contributor.author | Wong, Wai Shiu Fred | |
dc.date.accessioned | 2022-07-24T02:19:10Z | |
dc.date.available | 2022-07-24T02:19:10Z | |
dc.date.issued | 2019-06-01 | |
dc.identifier.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 | |
dc.identifier.issn | 14714892 | |
dc.identifier.issn | 14714973 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/229077 | |
dc.description.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. | |
dc.language.iso | en | |
dc.publisher | ELSEVIER SCI LTD | |
dc.source | Elements | |
dc.subject | Science & Technology | |
dc.subject | Life Sciences & Biomedicine | |
dc.subject | Pharmacology & Pharmacy | |
dc.subject | OBSTRUCTIVE PULMONARY-DISEASE | |
dc.subject | AIRWAY HYPERRESPONSIVENESS | |
dc.subject | CORTICOSTEROID SENSITIVITY | |
dc.subject | EPITHELIAL-CELLS | |
dc.subject | MOUSE MODELS | |
dc.subject | RESISTANCE | |
dc.subject | THEOPHYLLINE | |
dc.subject | EXPRESSION | |
dc.subject | EXACERBATIONS | |
dc.subject | INHIBITION | |
dc.type | Article | |
dc.date.updated | 2022-07-17T04:26:54Z | |
dc.contributor.department | PHARMACOLOGY | |
dc.description.doi | 10.1016/j.coph.2019.04.010 | |
dc.description.sourcetitle | CURRENT OPINION IN PHARMACOLOGY | |
dc.description.volume | 46 | |
dc.description.page | 73-81 | |
dc.published.state | Published | |
Appears in Collections: | Staff Publications Elements |
Show simple item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
Steroid Resistance Curr Opin Pharmacol 2019.pdf | 669.89 kB | Adobe PDF | CLOSED | None |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.