Endothelin, PAF and thromboxane A2 in allergic pulmonary hyperreactivity in mice

Richter, Martin; Cloutier, S.; Sirois, Pierré

doi:10.1016/j.plefa.2007.02.004

Cited by 6 publications

(3 citation statements)

References 38 publications

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“…We chose endothelin, trkb, and fractalkine because each has been shown to impact airway responsiveness in mice [52–55]. Adipsin was chosen because it is a member of the complement family of proteins and because complement has been shown to play a key role in airway responsiveness [56].…”

Section: Resultsmentioning

confidence: 99%

“…Data support a role for endothelin in other obesity-related conditions including hypertension and insulin resistance [89–92], and it is conceivable that increased pulmonary endothelin expression (Fig. 5A) contributes to obesity-related AHR: endothelin causes AHR when administered intranasally in mice [52], and endothelin receptor antagonists attenuate AHR induced by allergen sensitization and challenge [52, 53]. Furthermore, both obesity-related AHR and increases in endothelin mRNA were attenuated in TNFR2 −/− mice (Figs.…”

Section: Discussionmentioning

confidence: 99%

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Obesity and airway responsiveness: Role of TNFR2

Williams¹,

Chen²,

Kasahara³

et al. 2013

Pulmonary Pharmacology & Therapeutics

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Obese mice exhibit innate airway hyperresponsiveness (AHR), a feature of asthma. Tumor necrosis factor alpha (TNFα) is implicated in the disease progression and chronic inflammatory status of both obesity and asthma. TNF acts via two TNF receptors, TNFR1 and TNFR2. To examine the role of TNFR2 in the AHR observed in obese mice, we generated obese Cpefat mice that were either sufficient or deficient in TNFR2 (Cpefat and Cpefat/TNFR2−/− mice, respectively) and compared them with their lean controls (WT and TNFR2−/− mice). Compared to WT mice, Cpefat mice exhibited AHR to aerosolized methacholine (measured using the forced oscillation technique) which was ablated in Cpefat/TNFR2−/− mice. Bioplex or ELISA assay indicated significant increases in serum leptin, G-CSF, IL-7, IL-17A, TNFα, and KC in obese versus lean mice, as well as significant obesity-related increases in bronchoalveolar lavage fluid (BALF) G-CSF and IP-10, regardless of TNFR2 status. Importantly, BALF IL-17A was significantly increased over lean controls in Cpefat but not Cpefat/TNFR2−/− mice. Functional annotation clustering of significantly affected genes identified from microarray analysis comparing gene expression in lungs of Cpefat and WT mice, identified blood vessel morphogenesis as the gene ontology category most affected by obesity. This category included several genes associated with AHR, including endothelin and trkB. Obesity increased pulmonary mRNA expression of endothelin and trkB in TNFR2 sufficient but not deficient mice. Our results indicate that TNFR2 signaling is required for the innate AHR that develops in obese mice, and suggest that TNFR2 may act by promoting IL-17A, endothelin, and/or trkB expression.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Obesity and airway responsiveness: Role of TNFR2

Williams¹,

Chen²,

Kasahara³

et al. 2013

Pulmonary Pharmacology & Therapeutics

View full text Add to dashboard Cite

show abstract

“…By binding to PTAFR, its cognate receptor, PAF causes changes such as endothelial changes that can result in altered vasomotor tone, vascular permeability and chronic changes such as pulmonary vascular remodeling (10,(21)(22)(23). In addition to initiating localized inflammation on its own, PAF can produce effects such as increase in airway hyper-reactivity through the generation of eicosanoids such as thromboxane A2 and leukotrienes (24). Much of the role played by PAF in the pathogenesis of lung disorders such as chronic obstructive pulmonary disease, pulmonary fibrosis, asthma, and ARDS is mediated through its potent pro-inflammatory effects that include increased leukocyte adhesion, recruitment, chemotaxis, and degranulation.…”

Section: Discussionmentioning

confidence: 99%

Platelet Activating Factor Activity Modulates Hyperoxic Neonatal Lung Injury Severity

Yee

Kandasamy

Ambalavanan

et al. 2023

Preprint

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Hyperoxia-induced inflammation contributes significantly to developmental lung injury and bronchopulmonary dysplasia (BPD) in preterm infants. Platelet activating factor (PAF) is known to be a major driver of inflammation in lung diseases such as asthma and pulmonary fibrosis, but its role in BPD has not been previously investigated. Therefore, to determine whether PAF signaling independently modulates neonatal hyperoxic lung injury and BPD pathogenesis, lung structure was assessed in 14 day-old C57BL/6 wild-type (WT) and PAF receptor knockout (PTAFR KO) mice that were exposed to 21% (normoxia) or 85% O2 (hyperoxia) from postnatal day 4. Lung morphometry showed that PTAFR KO mice had attenuated hyperoxia-induced alveolar simplification when compared to WT mice. Functional analysis of gene expression data from hyperoxia-exposed vs. normoxia-exposed lungs of WT and PTAFR KO showed that the most upregulated pathways were the hypercytokinemia/hyperchemokinemia pathway in WT mice, NAD signaling pathway in PTAFR KO mice, and agranulocyte adhesion and diapedesis as well as other pro-fibrotic pathways such as tumor microenvironment and oncostatin-M signaling in both mice strains, indicating that PAF signaling may contribute to inflammation but may not be a significant mediator of fibrotic processes during hyperoxic neonatal lung injury. Gene expression analysis also indicated increased expression of pro-inflammatory genes such as CXCL1, CCL2 and IL-6 in the lungs of hyperoxia-exposed WT mice and metabolic regulators such as HMGCS2 and SIRT3 in the lungs of PTAFR KO mice, suggesting that PAF signaling may modulate BPD risk through changes in pulmonary inflammation and/or metabolic reprogramming in preterm infants.

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The role of endothelin pathway in modulation of airway reactivity to methacholine in C57Bl/6 and BALB/c mice

Landgraf

Jancar

2008

European Journal of Pharmacology

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Endothelin, PAF and thromboxane A2 in allergic pulmonary hyperreactivity in mice

Cited by 6 publications

References 38 publications

Obesity and airway responsiveness: Role of TNFR2

Obesity and airway responsiveness: Role of TNFR2

Platelet Activating Factor Activity Modulates Hyperoxic Neonatal Lung Injury Severity

The role of endothelin pathway in modulation of airway reactivity to methacholine in C57Bl/6 and BALB/c mice

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