The Interleukin-17 Induced Activation and Increased Survival of Equine Neutrophils Is Insensitive to Glucocorticoids.
Abstract: Glucocorticoids (GCs) are the most effective drugs for the treatment of human asthma. However, a subgroup of asthmatic patients with neutrophilic airway inflammation is insensitive to GCs. Interleukin-17 (IL-17), a cytokine upregulated in the airways of a subset of human asthmatic patients, contributes to the recruitment of neutrophils and induces a glucocorticoid resistance in human airway epithelial cells. We hypothesized that IL-17 similarly activates neutrophils and contributes to their persistence in the asthmatic airways in spite of glucocorticoid therapy. To determine whether IL-17 directly activates neutrophils and whether this response is attenuated by GCs. Neutrophils were isolated from the blood of horses and incubated in the presence of recombinant equine IL-17, LPS and dexamethasone. mRNA and protein expression of IL-17 receptors (IL-17RA/IL-17RC) were assessed by qPCR and immunoblot, respectively. Pro-inflammatory cytokine expression, cell viability and apoptosis were determined by qPCR, Trypan Blue exclusion test, and flow cytometry, respectively. Equine neutrophils express both IL-17RA and IL-17RC at the mRNA and protein levels. Neutrophil stimulation with IL-17 increases the mRNA expression of IL-8, which is not attenuated by dexamethasone (p = 0.409). Also, neutrophil viability is significantly increased (p<0.0001) by IL-17 in the presence of LPS when compared to LPS alone. Flow cytometry and light microscopy revealed that LPS-induced apoptosis is decreased by IL-17 (p = 0.02 and p = 0.006 respectively). These results indicate that IL-17 directly activates equine neutrophils at 24 hours, and that the expression of IL-8 thus induced is not attenuated by GCs. Additionally, IL-17 increases neutrophil viability and decreases apoptosis. These findings suggest an important role of IL-17 in pulmonary persistence of neutrophils in the asthmatic airways.
Publication Date: 2016-05-03 PubMed ID: 27138006PubMed Central: PMC4854453DOI: 10.1371/journal.pone.0154755Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research aimed to explore the impact of Interleukin-17 (IL-17) on the activation and survival of neutrophils in horses, particularly those with persistent neutrophilic airways despite undergoing glucocorticoid (GC) therapy. The study observed that IL-17 directly activates equine neutrophils, increases their lifespan, and lessens apoptosis.
Methodology
- The team initiated the research by hypothesizing that IL-17, a cytokine known to assist in the recruitment of neutrophils and develop glucocorticoid resistance, plays a substantial role in stimulating neutrophils and helps in their retention in asthmatic airways despite GC therapy.
- The researchers harvested neutrophils from horse blood and exposed them to recombinant equine IL-17, LPS and dexamethasone.
- They assessed the mRNA and protein expression levels of IL-17 receptors (IL-17RA/IL-17RC) using qPCR and immunoblot techniques.
- The experiment also evaluated pro-inflammatory cytokine expression, cell viability, and apoptosis. They made use of qPCR for pro-inflammatory cytokine expression, the Trypan Blue exclusion test for cellular viability, and flow cytometry for apoptosis.
Findings
- The researchers reported that equine neutrophils express both IL-17RA and IL-17RC at the mRNA and protein levels.
- They found that IL-17 stimulation improved the mRNA expression of IL-8, which was not lessened by dexamethasone.
- The study also showed that the presence of IL-17 significantly enhanced the life span of neutrophils (compared to LPS alone) when exposed to LPS.
- Through flow cytometry and light microscopy analysis, a decrease in LPS-induced apoptosis was noticed with IL-17.
Conclusion
- The research establishes that IL-17 has a direct activating effect on equine neutrophils at 24 hours. The induced expression of IL-8 was unaffected by GCs.
- Also, IL-17 was found to augment neutrophil viability while reducing apoptosis. These discoveries suggest that IL-17 may contribute significantly to the pulmonary persistence of neutrophils in the asthmatic airways.
Cite This Article
APA
Murcia RY, Vargas A, Lavoie JP.
(2016).
The Interleukin-17 Induced Activation and Increased Survival of Equine Neutrophils Is Insensitive to Glucocorticoids.
PLoS One, 11(5), e0154755.
https://doi.org/10.1371/journal.pone.0154755 Publication
Researcher Affiliations
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Q, Canada.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Q, Canada.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Q, Canada.
MeSH Terms
- Animals
- Apoptosis / drug effects
- Asthma / immunology
- Cell Survival / drug effects
- Dexamethasone / pharmacology
- Female
- Gene Expression Regulation / drug effects
- Glucocorticoids / pharmacology
- Horses
- Interleukin-17 / metabolism
- Neutrophils / cytology
- Neutrophils / drug effects
- Neutrophils / immunology
- Receptors, Interleukin-17 / metabolism
Conflict of Interest Statement
The authors have declared that no competing interests exist.
References
This article includes 40 references
Citations
This article has been cited 15 times.- Zhou Y, Qiu Y, Bao W, Han L, Xue Y, Zhang Y, Tian X, Fu Q, Lv C, Yin D, Zhang M. Evaluating the effects of vitamin D Level on airway obstruction in two asthma endotypes in humans and in two mouse models with different intake of vitamin D during early-life.. Front Immunol 2023;14:1107031.
- Gressler AE, Lübke S, Wagner B, Arnold C, Lohmann KL, Schnabel CL. Comprehensive Flow Cytometric Characterization of Bronchoalveolar Lavage Cells Indicates Comparable Phenotypes Between Asthmatic and Healthy Horses But Functional Lymphocyte Differences.. Front Immunol 2022;13:896255.
- Simões J, Batista M, Tilley P. The Immune Mechanisms of Severe Equine Asthma-Current Understanding and What Is Missing.. Animals (Basel) 2022 Mar 16;12(6).
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