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Respiratory research2017; 18(1); 207; doi: 10.1186/s12931-017-0689-4

Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma.

Abstract: Severe neutrophilic asthma is poorly responsive to glucocorticosteroids (GC). Neutrophil extracellular traps (NETs) within the lungs have been associated with the severity of airway obstruction and inflammation in asthma, and were found to be unaffected by GC in vitro. As IL-17 is overexpressed in neutrophilic asthma and contributes to steroid insensitivity in different cell types, we hypothesized that NETs formation in asthmatic airways would be resistant to GC through an IL-17 mediated pathway. Six neutrophilic severe asthmatic horses and six healthy controls were studied while being treated with dexamethasone. Lung function, bronchoalveolar lavage fluid (BALF) cytology and NETs formation, as well as the expression of CD11b and CD13 by blood and airway neutrophils were evaluated. The expression of IL-17 and its role in NETs formation were also studied. Airway neutrophils from asthmatic horses, as opposed to blood neutrophils, enhanced NETs formation, which was then decreased by GC. GC also tended to decrease the expression of CD11b in blood neutrophils, but not in airway neutrophils. IL-17 mRNA was increased in BALF cells of asthmatic horses and was unaffected by GC. However, both GC and IL-17 inhibited NETs formation in vitro. GC decreased NETs formation in vitro and also in vivo in the lungs of asthmatic horses. However, airway neutrophil activation during asthmatic inflammation was otherwise relatively insensitive to GC. The contribution of IL-17 to these responses requires further study.
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Publication Date: 2017-12-12 PubMed ID: 29233147PubMed Central: PMC5727947DOI: 10.1186/s12931-017-0689-4Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research examines the effect of glucocorticosteroids (a kind of drug) on the structures called neutrophil extracellular traps in the lungs of horses that have a severe type of asthma. The findings suggest that glucocorticosteroids lessen the formation of these structures in the lungs but do not necessarily influence the behaviour of specific immune cells in the lungs.

Study Design and Purpose

  • The aim of this research was to investigate how neutrophil extracellular traps (NETs) behave in the presence of glucocorticosteroids (GC). NETs are DNA structures released by neutrophils, a type of white blood cell, to trap and kill pathogens. However, in a severe form of asthma often observed in horses, these NETs contribute to airway obstruction and inflammation.
  • The research sought to understand if GC treatment is effective in managing inflammatory parameters associated with neutrophilic severe asthma. Specifically, the study aimed to discover if GC could decrease the formation of NETs, especially considering that a protein called IL-17 believed to be overexpressed in neutrophilic asthma can contribute to steroid (like GC) insensitivity.

Research Methodology

  • The study involved twelve horses in total, six of which were severely asthmatic and the other six were healthy controls. All were treated with dexamethasone, a type of GC.
  • The researchers used various types of measurements to understand GC’s impact on NET generation and other inflammatory parameters. They investigated lung function, conducted bronchoalveolar lavage fluid (BALF) cytology (examination of cell types), measured NETs formation, and analysed the expression of certain proteins (CD11b and CD13) in blood and airway neutrophils.
  • The expression of IL-17 was also considered both in BALF cells and in NET formation.

Results

  • The results showed that when horses had asthmatic inflammation, their airway neutrophils significantly boosted the formation of NETs compared to their blood neutrophils.
  • This increased formation of NETs was successfully downregulated by GC treatment. However, the GC therapy did not notably impact the activation of airway neutrophils, indicating that certain aspects of airway neutrophil activation during asthma are insensitive to GC.
  • GC also lowered the expression of the protein CD11b in blood neutrophils, but not in airway neutrophils.
  • Another important finding was that the expression of IL-17 in BALF cells significantly increased in asthmatic horses. Surprisingly, GC did not appear to influence IL-17 expression. Still, both IL-17 and GC inhibited the formation of NETs in a controlled in vitro environment.

Conclusion

  • This research concluded that GC can induce a decrease in NETs formation both in vitro (lab test tubes) and in vivo (in the living organism, here, the lungs of asthmatic horses).
  • However, this study notes that the airway neutrophil activation, which is a significant aspect of asthma, was mostly unaffected by GC treatment. This implies that further research is required to comprehend the complex dynamics of neutrophil activity, NETs generation, and GC interaction, especially considering the role of IL-17.

Cite This Article

APA
Vargas A, Boivin R, Cano P, Murcia Y, Bazin I, Lavoie JP. (2017). Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma. Respir Res, 18(1), 207. https://doi.org/10.1186/s12931-017-0689-4

Publication

Respiratory research
ISSN: 1465-993X
NlmUniqueID: 101090633
Country: England
Language: English
Volume: 18
Issue: 1
Pages: 207
PII: 207

Researcher Affiliations

Vargas, Amandine
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, 3200, rue Sicotte, Saint-Hyacinthe, Q, J2S 2M2, Canada.
Boivin, Roxane
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, 3200, rue Sicotte, Saint-Hyacinthe, Q, J2S 2M2, Canada.
Cano, Patricia
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, 3200, rue Sicotte, Saint-Hyacinthe, Q, J2S 2M2, Canada.
Murcia, Yoana
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, 3200, rue Sicotte, Saint-Hyacinthe, Q, J2S 2M2, Canada.
Bazin, Isabelle
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, 3200, rue Sicotte, Saint-Hyacinthe, Q, J2S 2M2, Canada.
Lavoie, Jean-Pierre
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, 3200, rue Sicotte, Saint-Hyacinthe, Q, J2S 2M2, Canada. jean-pierre.lavoie@umontreal.ca.

MeSH Terms

  • Animals
  • Asthma / drug therapy
  • Asthma / metabolism
  • Asthma / pathology
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Extracellular Traps / drug effects
  • Extracellular Traps / metabolism
  • Female
  • Glucocorticoids / pharmacology
  • Glucocorticoids / therapeutic use
  • Horses
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Neutrophils / pathology

Conflict of Interest Statement

ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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