| Targeting phosphoinositide 3-kinase δ for allergic asthma. | |
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MedLine Citation:
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PMID: 22260698 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Chronic inflammation in the lung has long been linked to the pathogenesis of asthma. Central to this airway inflammation is a T-cell response to allergens, with Th2 cytokines driving the differentiation, survival and function of the major inflammatory cells involved in the allergic cascade. PI3Kδ (phosphoinositide 3-kinase δ) is a lipid kinase, expressed predominantly in leucocytes, where it plays a critical role in immune receptor signalling. A selective PI3Kδ inhibitor is predicted to block T-cell activation in the lung, reducing the production of pro-inflammatory Th2 cytokines. PI3Kδ is also involved in B-cell and mast cell activation. Therefore the inhibition of PI3Kδ should dampen down the inflammatory cascade involved in the asthmatic response through a wide breadth of pharmacology. Current anti-inflammatory therapies, which are based on corticosteroids, are effective in controlling inflammation in mild asthmatics, but moderate/severe asthmatic patients remain poorly controlled, experiencing recurrent exacerbations. Corticosteroids have no effect on mast cell degranulation and do not act directly on B-cells, so, overall, a PI3Kδ inhibitor has the potential to deliver improvements in onset of action, efficacy and reduced exacerbations in moderate/severe asthmatics. Additionally, PI3Kδ inhibition is expected to block effects of Th17 cells, which are increasingly implicated in steroid-insensitive asthma. |
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Authors:
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Wendy C Rowan; Janet L Smith; Karen Affleck; Augustin Amour |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Biochemical Society transactions Volume: 40 ISSN: 1470-8752 ISO Abbreviation: Biochem. Soc. Trans. Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-01-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7506897 Medline TA: Biochem Soc Trans Country: England |
Other Details:
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Languages: eng Pagination: 240-5 Citation Subset: IM |
Affiliation:
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*Biological Reagents and Assay Development, Platform Technology and Science, GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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