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Series GSE249135 Query DataSets for GSE249135
Status Public on Mar 13, 2024
Title Effect of group III phospholipase A2 deletion on gene expression in bronchial epithelial cells in an antigen-induced asthma model.
Organism Mus musculus
Experiment type Expression profiling by array
Summary Asthma is a chronic inflammatory disease of the airways characterized by recurrent episodes of airway obstruction, hyperresponsiveness, remodeling, and eosinophilia. Phospholipase A2s (PLA2s), which release fatty acids and lysophospholipids from membrane phospholipids, have been implicated in exacerbating asthma by generating pro-asthmatic lipid mediators, but an understanding of the association between individual PLA2 subtypes and asthma is still incomplete. Here, we show that group III secreted PLA2 (sPLA2-III) plays an ameliorating, rather than aggravating, role in asthma pathology. In both mouse and human lungs, sPLA2-III was expressed in bronchial epithelial cells and decreased during the asthmatic response. In an ovalbumin (OVA)-induced asthma model, Pla2g3 knockout (-/-) mice exhibited enhanced airway hyperresponsiveness, eosinophilia, OVA-specific IgE production, and type 2 cytokine expression as compared to Pla2g3 wild-type (+/+) mice. Lipidomics analysis showed that the pulmonary levels of several lysophospholipids, including lysophosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidic acid (LPA), were decreased in OVA-challenged Pla2g3-/- mice relative to Pla2g3+/+ mice. LPA receptor 2 agonists suppressed thymic stromal lymphopoietin expression in bronchial epithelial cells and reversed airway hyperresponsiveness and eosinophilia in Pla2g3-/- mice, suggesting that sPLA2-III negatively regulates allergen-induced asthma at least by producing LPA. Thus, the activation of the sPLA2-III-LPA pathway may be a new therapeutic target for allergic asthma.
Microarray gene profiling of the bronchial epithelial cells isolated from OVA-challenged lung revealed the increased expression of various chemokines and type 2 epithelial cytokines in bronchial epithelial cells from Pla2g3-/- mice as compared to those from Pla2g3+/+ mice following OVA challenge.
Overall design Model, antigen (OVA)-induced asthma. Mice were sensitized with intraperitoneal injections of ovalbumin (10 µg) plus 1.3 mg of aluminum hydroxide (alum adjuvant) on days 0 and 14. On days 26, 27, and 28, the mice were challenged with 1% OVA aeroallergen for 30 min per day.; Cells, bronchial epithelial cells isolated from mouse lung; Groups, Pla2g3 knockout (–/–) and wild-type (+/+); Condiotion, 3 h after final antigen challenge versus control; RNA, total RNA samples pooled from four samples.
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Contributor(s) Hamu-Tanoue A, Taketomi Y, Nishito Y, Inoue H, Murakami M
Citation(s) 38236184
Submission date Dec 01, 2023
Last update date Jun 17, 2024
Contact name Yoshitaka Taketomi
Organization name The University of Tokyo
Department CDBIM, Graduate School of Medicine,
Lab Laboratory of Microenvironmental Metabolic Health Science
Street address 7-3-1 Hongo, Bunkyo-ku,
City Tokyo
ZIP/Postal code 113-8655
Country Japan
Platforms (1)
GPL10333 Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Feature Number version)
Samples (4)
GSM7927225 Pla2g3+/+, control, bronchial epithelial cells
GSM7927226 Pla2g3-/-, control, bronchial epithelial cells
GSM7927227 Pla2g3+/+, antigen challenged, bronchial epithelial cells
BioProject PRJNA1047532

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Supplementary file Size Download File type/resource
GSE249135_RAW.tar 42.1 Mb (http)(custom) TAR (of TXT)

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