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Molecular Mechanisms Underlying Glucocorticoid Insensitivity in Asthma

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 3798

Special Issue Editor

Joint Health Science Center, School of Veterinary Medicine, Rowan University, 201 Broadway, Camden, NJ 08103, USA
Interests: airway inflammation-related research; pharmacological aspects of pulmonary diseases; airway smooth muscle (ASM) biology; glucocorticoid (GC) signaling; glucocorticoid insensitivity

Special Issue Information

Dear Colleagues,

Although in most patients with asthma, symptoms are well controlled by inhaled glucocorticoids (GCs), a subgroup of patients suffering from severe asthma respond poorly to GC therapy. Such GC insensitivity (GCI) represents a profound challenge in managing patients with asthma. Even though GCI in patients with severe asthma has been investigated by several groups, uncertainty exists regarding the underlying molecular mechanisms. In asthma, airway structural cells are among the targets of GC therapy and have emerged as key contributors not only to bronchoconstriction, but also to airway inflammation and remodeling, as implied by experimental and clinical evidence. This issue aims to foster studies investigating the molecular mechanisms underlying the impairment of GC actions both in immune cells such as T cells, macrophages, eosinophils and neutrophils and in non-immune cells, such as airway fibroblasts, lung epithelial cells and airway smooth muscle cells.

Dr. Omar Tliba
Guest Editor

Manuscript Submission Information

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Keywords

  • airway remodeling
  • airway inflammation
  • asthma
  • steroid resistance
  • airway smooth muscle
  • airway epithelial cells
  • lung fibroblasts
  • glucocorticoid insensitivity

Published Papers (2 papers)

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Review

14 pages, 971 KiB  
Review
Aging-Related Mechanisms Contribute to Corticosteroid Insensitivity in Elderly Asthma
by Maria L. Ford, Anushka Ruwanpathirana, Brandon W. Lewis and Rodney D. Britt, Jr.
Int. J. Mol. Sci. 2023, 24(7), 6347; https://doi.org/10.3390/ijms24076347 - 28 Mar 2023
Cited by 4 | Viewed by 1410
Abstract
Asthma in elderly populations is an increasing health problem that is accompanied by diminished lung function and frequent exacerbations. As potent anti-inflammatory drugs, corticosteroids are commonly used to reduce lung inflammation, improve lung function, and manage disease symptoms in asthma. Although effective for [...] Read more.
Asthma in elderly populations is an increasing health problem that is accompanied by diminished lung function and frequent exacerbations. As potent anti-inflammatory drugs, corticosteroids are commonly used to reduce lung inflammation, improve lung function, and manage disease symptoms in asthma. Although effective for most individuals, older patients are more insensitive to corticosteroids, making it difficult to manage asthma in this population. With the number of individuals older than 65 continuing to increase, it is important to understand the distinct mechanisms that promote corticosteroid insensitivity in the aging lung. In this review, we discuss corticosteroid insensitivity in asthma with an emphasis on mechanisms that contribute to persistent inflammation and diminished lung function in older individuals. Full article
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18 pages, 1162 KiB  
Review
Glucocorticoid Insensitivity in Asthma: The Unique Role for Airway Smooth Muscle Cells
by Patricia Ramos-Ramírez and Omar Tliba
Int. J. Mol. Sci. 2022, 23(16), 8966; https://doi.org/10.3390/ijms23168966 - 11 Aug 2022
Cited by 7 | Viewed by 1800
Abstract
Although most patients with asthma symptoms are well controlled by inhaled glucocorticoids (GCs), a subgroup of patients suffering from severe asthma respond poorly to GC therapy. Such GC insensitivity (GCI) represents a profound challenge in managing patients with asthma. Even though GCI in [...] Read more.
Although most patients with asthma symptoms are well controlled by inhaled glucocorticoids (GCs), a subgroup of patients suffering from severe asthma respond poorly to GC therapy. Such GC insensitivity (GCI) represents a profound challenge in managing patients with asthma. Even though GCI in patients with severe asthma has been investigated by several groups using immune cells (peripheral blood mononuclear cells and alveolar macrophages), uncertainty exists regarding the underlying molecular mechanisms in non-immune cells, such as airway smooth cells (ASM) cells. In asthma, ASM cells are among the targets of GC therapy and have emerged as key contributors not only to bronchoconstriction but also to airway inflammation and remodeling, as implied by experimental and clinical evidence. We here summarize the current understanding of the actions/signaling of GCs in asthma, and specifically, GC receptor (GR) “site-specific phosphorylation” and its role in regulating GC actions. We also review some common pitfalls associated with studies investigating GCI and the inflammatory mediators linked to asthma severity. Finally, we discuss and contrast potential molecular mechanisms underlying the impairment of GC actions in immune cells versus non-immune cells such as ASM cells. Full article
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