IgE mediates broncho-vascular remodeling after neonatal sensitization in mice

Chetty, Anne; Cao, Gong-Jie; Sharda, Azeem; Tsay, T; Nielsen, Heber C.

doi:10.2741/e773

Cited by 3 publications

(1 citation statement)

References 26 publications

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“…Mice sensitized to HDM developed significant reactive airway disease, seen as a progressively increasing airway resistance in response to increasing MCh doses. 11 , 13 , 16 As expected, mice which received no HDM exposure exhibited a modest dose-dependent increase in airway resistance in response to MCh. Moreover, exposure to GC021109 alone (no HDM sensitization) did not significantly affect the MCh response.…”

Section: Resultssupporting

confidence: 70%

A purinergic P2Y6 receptor agonist prodrug modulates airway inflammation, remodeling, and hyperreactivity in a mouse model of asthma

Chetty¹,

Sharda²,

Warburton³

et al. 2018

JAA

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BackgroundPurinergic receptors control cell proliferation, apoptosis, migration, inflammation, and cytokine secretion. Increased expression of specific purinergic receptors is reported in asthma. The role of purinergic P2Y6 receptors (P2Y6R) in asthma is controversial.HypothesisP2Y6R activation in asthma improves pulmonary function and reduces inflammation and smooth muscle amount.MethodsFemale mice (C57/BL6, age 30 days) were randomly assigned to receive intranasal house dust mite (HDM) antigen (40 or 80 µg) or saline, 5 days/week, for 6 weeks. Randomly selected subgroups received intraperitoneal P2Y6R agonist prodrug (GC021109; 10 or 100 µg/kg weight/dose) simultaneously with HDM. After 6 weeks, lung function was measured. Lung lavage fluid (LLF) was used to measure total cell count, total protein, and cytokines. Immunohistochemistry for alpha smooth muscle actin (α-SMA) was done. Airway wall thickness was measured on micro-computed tomography (micro-CT) images.ResultsPulmonary function testing revealed a HDM dose-dependent airway hyperresponsiveness. Airway resistance was increased 2-fold while compliance was decreased by 50% at the higher HDM dose (P<0.05). GC021109 prevented these changes. HDM-exposed mice had elevated inflammatory cell and total protein levels in LLF which were prevented by GC021109 (P<0.05). HDM mice also had elevated LLF levels of interleukin (IL)-4, IL-5, IL-12, granulocyte colony stimulating factor, chemokine (C-X-C) motif ligand 1, and leukemia inhibitory factor that were reduced by GC021109 with a dose-dependent pattern. HDM mice had increased peribronchial and perivascular inflammatory cell infiltration and increased α-SMA; these changes were absent with GC021109. Airway wall thickness measured on micro-CT images was increased after HDM exposure and significantly reduced by GC021109 treatment.ConclusionThe P2Y6R prodrug GC021109 inhibited allergen-induced changes in pulmonary function, inflammatory responses, and airway and vascular smooth muscle mass. P2Y6R activation may be an effective therapeutic maintenance strategy in asthma.

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Section: Resultssupporting

confidence: 70%

A purinergic P2Y6 receptor agonist prodrug modulates airway inflammation, remodeling, and hyperreactivity in a mouse model of asthma

Chetty¹,

Sharda²,

Warburton³

et al. 2018

JAA

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Airway remodeling: The Drosophila model permits a purely epithelial perspective

et al. 2022

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Airway remodeling is an umbrella term for structural changes in the conducting airways that occur in chronic inflammatory lung diseases such as asthma or chronic obstructive pulmonary disease (COPD). The pathobiology of remodeling involves multiple mesenchymal and lymphoid cell types and finally leads to a variety of hardly reversible changes such as hyperplasia of goblet cells, thickening of the reticular basement membrane, deposition of collagen, peribronchial fibrosis, angiogenesis and hyperplasia of bronchial smooth muscle cells. In order to develop solutions for prevention or innovative therapies, these complex processes must be understood in detail which requires their deconstruction into individual building blocks. In the present manuscript we therefore focus on the role of the airway epithelium and introduce Drosophila melanogaster as a model. The simple architecture of the flies' airways as well as the lack of adaptive immunity allows to focus exclusively on the importance of the epithelium for the remodeling processes. We will review and discuss genetic and environmentally induced changes in epithelial structures and molecular responses and propose an integrated framework of research for the future.

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IgE regulates airway smooth muscle phenotype: Future perspectives in allergic asthma

Redhu¹,

Gounni²

2015

WJI

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IgE mediates broncho-vascular remodeling after neonatal sensitization in mice

Cited by 3 publications

References 26 publications

A purinergic P2Y6 receptor agonist prodrug modulates airway inflammation, remodeling, and hyperreactivity in a mouse model of asthma

A purinergic P2Y6 receptor agonist prodrug modulates airway inflammation, remodeling, and hyperreactivity in a mouse model of asthma

Airway remodeling: The Drosophila model permits a purely epithelial perspective

IgE regulates airway smooth muscle phenotype: Future perspectives in allergic asthma

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