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Singlet oxygen -derived nerve growth factor exacerbates airway hyperresponsiveness in a mouse model of asthma with mixed inflammation. | LitMetric

AI Article Synopsis

  • - The study investigates the interaction between nerve growth factor (NGF) and neutrophils in refractory asthma, highlighting their role in airway hyperresponsiveness (AHR) and bronchial inflammation.
  • - Researchers established a mouse model of asthma (Mix-in) to observe higher levels of NGF and neuroinflammation compared to typical eosinophilic asthma, noting that NGF production increased with elevated singlet oxygen levels from neutrophil activity.
  • - Results indicate that targeting the NGF and neutrophil interaction could lead to new treatment options and biomarkers for non-type 2 refractoriness in asthma.

Article Abstract

Background: Refractory asthma, which is caused by several factors including neutrophil infiltration is a serious complication of bronchial asthma. We previously reported that nerve growth factor (NGF) is involved in AHR. NGF-derived induction of hyperalgesia is dependent on neutrophils; however, this relationship remains unclear in respiratory disease. In this study, we examined the roles of neutrophils and NGF in refractory asthma.

Methods: Using intranasal house dust mite sensitization, we established a mouse model of asthma with mixed inflammation (Mix-in). AHR, NGF production and hyperinnervation of the lungs were examined with or without different inhibitory treatments. The levels of the singlet oxygen markers, 10- and 12-(Z,E)-hydroxyoctadecadienoic acids (HODE) in the lungs, were measured by liquid chromatography-tandem mass spectrometry. An in vitro experiment was also performed to evaluate the direct effect of singlet oxygen on NGF production.

Results: NGF production and hyperinnervation were higher in Mix-in mice than in conventional eosinophilic-asthmatic mice and were positively correlated with AHR. Asthmatic parameters were inhibited by NGF neutralizing Abs and myeloperoxidase (MPO) inhibition. The 10- and 12-(Z,E)-HODEs levels were increased in the lungs and were positively correlated with MPO activity and NGF production. NGF was produced by bronchial epithelial cells in vitro upon stimulation with singlet oxygen.

Conclusions: Our findings suggest that neutrophil MPO-derived singlet oxygen induces increased NGF production, leading to AHR and 10- and 12-(Z,E)-HODEs production. These findings may help to develop new therapies targeting this mechanism and to establish a new biomarker for non-type 2 and refractory asthma.

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Source
http://dx.doi.org/10.1016/j.alit.2022.02.005DOI Listing

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