Targeting phosphoinositide 3-kinase δ for allergic asthma.

@article{Rowan2012TargetingP3,
  title={Targeting phosphoinositide 3-kinase $\delta$ for allergic asthma.},
  author={Wendy C. Rowan and Janet L. Smith and Karen Affleck and Augustin Amour},
  journal={Biochemical Society transactions},
  year={2012},
  volume={40 1},
  pages={
          240-5
        }
}
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… 
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Methods Citations
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32 Citations

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Citation Type

Targeting phosphoinositide 3‐kinase δ for the treatment of respiratory diseases
TLDR
The observation that inhibition of PI3Kδ may restore steroid effectiveness under conditions of oxidative stress is of particular interest for the treatment of severe respiratory disease, and targeting the PI3kδ pathway could reduce the incidence of pathogen‐induced exacerbations by improving macrophage‐mediated bacterial clearance.
PI3Kδ inhibition prevents IL33, ILC2s and inflammatory eosinophils in persistent airway inflammation
TLDR
It is shown that PI3Kδ inhibition dampens allergic inflammatory responses by ablating key cell types and cytokines involved in T-helper-2-driven inflammatory responses.
Aldose Reductase Inhibition Prevents Allergic Airway Remodeling through PI3K/AKT/GSK3β Pathway in Mice
TLDR
It is demonstrated that allergen-induced airway remodeling is mediated by AR and its inhibition blocks the progression of remodeling via inhibiting TGFβ1-induced Smad-independent and PI3K/AKT/GSK3β-dependent pathway.
PI3K signalling in inflammation.
Epithelial PI3K-δ Promotes House Dust Mite-Induced Allergic Asthma in NLRP3 Inflammasome-Dependent and -Independent Manners
TLDR
The results of this study suggest that PI3K-δ-isoform can promote HDM-induced allergic airway inflammation via NLRP3 inflammasome-dependent response as well as viaNLRP3Inflammation-independent epithelial cell activation.
Pharmacological targeting of allergen-specific T lymphocytes.
Design and Synthesis of Soluble and Cell-Permeable PI3Kδ Inhibitors for Long-Acting Inhaled Administration.
TLDR
The identification of inhibitors based on a thiazolopyridone core structure and their subsequent optimization for inhalation are described, finding compounds with good lung retention and cell potency that could be taken forward to in vivo studies where significant target engagement could be demonstrated.
Epigenetic regulation of airway inflammation in asthma
TLDR
Maternal asthma during pregnancy is associated with alterations in peripheral blood DNA methylation in infants’ and Inflammatory phenotypes of asthma are associated with differential DNAmethylation in peripheralBlood monocytes, suggesting possible implications in the disease pathogenesis.
Research Advances on Selective Phosphatidylinositol 3 Kinase δ (PI3Kδ) Inhibitors.
Isoform-Selective PI3K Inhibitors for Various Diseases.
TLDR
This review summarizes the progress of isoform-selective PI3K inhibitors in preclinical and early clinical studies for anticancer and other various diseases.
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References

SHOWING 1-10 OF 26 REFERENCES
Phosphoinositide 3-kinase-δ inhibitor reduces vascular permeability in a murine model of asthma
Inhibition of phosphoinositide 3‐kinase δ attenuates allergic airway inflammation and hyperresponsiveness in murine asthma model
TLDR
It is implicate that inhibition of p110δ signaling pathway may have therapeutic potential for the treatment of allergic airway inflammation and hyperresponsiveness in murine asthma model.
Essential role for the p110δ phosphoinositide 3-kinase in the allergic response
TLDR
It is reported that genetic or pharmacological inactivation of the p110δ isoform of PI(3)K in mast cells leads to defective SCF-mediated in vitro proliferation, adhesion and migration, and to impaired allergen–IgE-induced degranulation and cytokine release.
Mechanisms and implications of phosphoinositide 3-kinase delta in promoting neutrophil trafficking into inflamed tissue.
TLDR
It is reported here that p110 delta is present in endothelial cells and participates in neutrophil trafficking by modulating the proadhesive state of these cells in response to tumor necrosis factor alpha (TNF alpha).
A role for phosphoinositol 3-kinase delta in the impairment of glucocorticoid responsiveness in patients with chronic obstructive pulmonary disease.
Isoform-Specific Functions of Phosphoinositide 3-Kinases: p110δ but Not p110γ Promotes Optimal Allergic Responses In Vivo1
TLDR
It is confirmed that both PI3K isoforms play an important role in FcεRI-activated mast cell degranulation in vitro, but only p110δ was found to be required for optimal IgE/Ag-dependent hypersensitivity responses in mice.
Pathogenesis of Asthma
  • S. Holgate
  • Biology, Medicine
    Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
  • 2008
TLDR
Increased focus on environmental factors beyond allergic exposure (such as virus infection, air pollution, and diet) are identifying targets in structural as well as immune and inflammatory cells at which to direct new interventions in asthma.
Selective role of PI3Kδ in neutrophil inflammatory responses
PI3K in lymphocyte development, differentiation and activation
TLDR
New insights into the role of PI3Ks in lymphocyte biology have been derived from gene-targeting studies, which have identified thePI3K subunits that are involved in B-cell and T-cell signalling.
Requirement for Phosphoinositide 3-Kinase p110δ Signaling in B Cell Antigen Receptor-Mediated Antigen Presentation1
TLDR
A role for p110δ signaling in B cell Ag presentation function is demonstrated, implicating 3-phosphoinositides and their targets in the latter stages of this process.
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