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Targeting phosphoinositide 3-kinase δ for the treatment of respiratory diseases.
- Source :
-
Annals of the New York Academy of Sciences [Ann N Y Acad Sci] 2013 Mar; Vol. 1280, pp. 35-9. - Publication Year :
- 2013
-
Abstract
- Asthma and chronic obstructive pulmonary disease (COPD) are characterized in their pathogenesis by chronic inflammation in the airways. Phosphoinositide 3-kinase δ (PI3Kδ), a lipid kinase expressed predominantly in leukocytes, is thought to hold much promise as a therapeutic target for such inflammatory conditions. Of particular interest for the treatment of severe respiratory disease is the observation that inhibition of PI3Kδ may restore steroid effectiveness under conditions of oxidative stress. PI3Kδ inhibition may also prevent recruitment of inflammatory cells, including T lymphocytes and neutrophils, as well as the release of proinflammatory mediators, such as cytokines, chemokines, reactive oxygen species, and proteolytic enzymes. In addition, targeting the PI3Kδ pathway could reduce the incidence of pathogen-induced exacerbations by improving macrophage-mediated bacterial clearance. In this review, we discuss the potential and highlight the unknowns of targeting PI3Kδ for the treatment of respiratory disease, focusing on recent developments in the role of the PI3Kδ pathway in inflammatory cell types believed to be critical to the pathogenesis of COPD.<br /> (© 2013 New York Academy of Sciences.)
- Subjects :
- Asthma enzymology
Epithelial Cells metabolism
Humans
Inflammation metabolism
Isoenzymes antagonists & inhibitors
Isoenzymes metabolism
Macrophages metabolism
Molecular Targeted Therapy
Neutrophils metabolism
Oxidative Stress
Phosphatidylinositol 3-Kinases metabolism
Pulmonary Disease, Chronic Obstructive enzymology
Reactive Oxygen Species metabolism
T-Lymphocytes metabolism
Asthma drug therapy
Phosphoinositide-3 Kinase Inhibitors
Pulmonary Disease, Chronic Obstructive drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1749-6632
- Volume :
- 1280
- Database :
- MEDLINE
- Journal :
- Annals of the New York Academy of Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 23551101
- Full Text :
- https://doi.org/10.1111/nyas.12039