ArticleExperimental & molecular medicine2018
PI3Kδ contributes to ER stress-associated asthma through ER-redox disturbances: the involvement of the RIDD-RIG-I-NF-κB axis.
Article in Experimental & molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 38 citations in OpenAlex.
- Single-nucleus RNA sequencing identifies conserved structural cell programs in allergic lung inflammation.The journal of allergy and clinical immunology. Global · 2026Article
- Hydroxyurea induces an oxidative stress response that triggers ER expansion and cytoplasmic protein aggregation.PLoS biology · 2025Article
- Dietary saturated fatty acids promote lung myeloid cell inflammasome activation and IL-1β-mediated inflammation in mice and humans.Science translational medicine · 2025Article
- In Vivo Study of Organ and Tissue Stability According to the Types of Bioresorbable Bone Screws.Materials (Basel, Switzerland) · 2024Article
- Distinctive CD39Nature communications · 2024Article
- Tumorous IRE1α facilitates CD8Cell communication and signaling : CCS · 2024Article
- Article
- Ameliorative Effect of Citrus Lemon Peel Extract and Resveratrol on Premature Ovarian Failure Rat Model: Role of iNOS/Caspase-3 Pathway.Molecules (Basel, Switzerland) · 2022Article
- NF-κB and its crosstalk with endoplasmic reticulum stress in atherosclerosis.Frontiers in cardiovascular medicine · 2022Review
- Saturated fatty acids entrap PDX1 in stress granules and impede islet beta cell function.Diabetologia · 2021Article
- Mechanisms Targeting the Unfolded Protein Response in Asthma.American journal of respiratory cell and molecular biology · 2021Review
- Phosphatidylinositol 3-kinase-δ controls endoplasmic reticulum membrane fluidity and permeability in fungus-induced allergic inflammation in mice.British journal of pharmacology · 2020Article
- Update on the role of endoplasmic reticulum stress in asthma.American journal of translational research · 2020Review
- Inhibition of PI3Kδ Enhances Poly I:C-Induced Antiviral Responses and Inhibits Replication of Human Metapneumovirus in Murine Lungs and Human Bronchial Epithelial Cells.Frontiers in immunology · 2020Article
- Regulation of IL-17A and implications for TGF-β1 comodulation of airway smooth muscle remodeling in severe asthma.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Potential Application ofNutrients · 2018Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperactivation of phosphoinositol 3-kinase (PI3K) has been suggested to be a potential mechanism for endoplasmic reticulum (ER) stress-enhanced airway hyperresponsiveness, and PI3K inhibitors have been examined as asthma therapeutics. However, the regulatory mechanism linking PI3K to ER stress and related pathological signals in asthma have not been defined. To elucidate these pathogenic pathways, we investigated the influence of a selective PI3Kδ inhibitor, IC87114, on airway inflammation in an ovalbumin/lipopolysaccharide (OVA/LPS)-induced asthma model. In OVA/LPS-induced asthmatic mice, the activity of PI3K, downstream phosphorylation of AKT and activation of nuclear factor-κB (NF-κB) were all significantly elevated; these effects were reversed by IC87114. IC87114 treatment also reduced the OVA/LPS-induced ER stress response by enhancing the intra-ER oxidative folding status through suppression of protein disulfide isomerase activity, ER-associated reactive oxygen species (ROS) accumulation and NOX4 activity. Furthermore, inositol-requiring enzyme-1α (IRE1α)-dependent degradation (RIDD) of IRE1α was reduced by IC87114, resulting in a decreased release of proinflammatory cytokines from bronchial epithelial cells. These results suggest that PI3Kδ may induce severe airway inflammation and hyperresponsiveness by activating NF-κB signaling through ER-associated ROS and RIDD-RIG-I activation. The PI3Kδ inhibitor IC87114 is a potential therapeutic agent against neutrophil-dominant asthma.
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