Differential Gene Expression Profiles and Selected Cytokine Protein Analysis of Mediastinal Lymph Nodes of Horses with Chronic Recurrent Airway Obstruction (RAO) Support an Interleukin-17 Immune Response.
Abstract: Recurrent airway obstruction (RAO) is a pulmonary inflammatory condition that afflicts certain mature horses exposed to organic dust particulates in hay. Its clinical and pathological features, manifested by reversible bronchoconstriction, excessive mucus production and airway neutrophilia, resemble the pulmonary alterations that occur in agricultural workers with occupational asthma. The immunological basis of RAO remains uncertain although its chronicity, its localization to a mucosal surface and its domination by a neutrophilic, non-septic inflammatory response, suggest involvement of Interleukin-17 (IL-17). We examined global gene expression profiles in mediastinal (pulmonary-draining) lymph nodes isolated from RAO-affected and control horses. Differential expression of > 200 genes, coupled with network analysis, supports an IL-17 response centered about NF-κB. Immunohistochemical analysis of mediastinal lymph node sections demonstrated increased IL-17 staining intensity in diseased horses. This result, along with the finding of increased IL-17 concentrations in lymph node homogenates from RAO-affected horses (P = 0.1) and a down-regulation of IL-4 gene and protein expression, provides additional evidence of the involvement of IL-17 in the chronic stages of RAO. Additional investigations are needed to ascertain the cellular source of IL-17 in this equine model of occupational asthma. Understanding the immunopathogenesis of this disorder likely will enhance the development of therapeutic interventions beneficial to human and animal pulmonary health.
Publication Date: 2015-11-12 PubMed ID: 26561853PubMed Central: PMC4642978DOI: 10.1371/journal.pone.0142622Google Scholar: Lookup
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Summary
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The research investigates the role of Interleukin-17 (IL-17) in recurrent airway obstruction (RAO), a chronic inflammatory respiratory condition in horses that resembles occupational asthma in humans. It uncovers that IL-17, alongside some other factors, might be involved in the chronic stages of RAO with evidence found in gene expression profiles and cytokine analysis.
Exploring the Causes of Recurrent Airway Obstruction (RAO)
- The research focuses on RAO, a health condition affecting mature horses, which is characterized by bronchoconstriction, excessive mucus production, and airway neutrophilia. These conditions closely resemble the symptoms of occupational asthma in humans, particularly those working in agriculture.
- The actual cause of RAO remains elusive and this research aims to investigate its immunological basis. The chronic nature of RAO, its manifestation onto a mucosal surface and its domination by a neutrophilic, non-septic inflammatory response, suggest the involvement of a molecule known as Interleukin-17 (IL-17).
Role of Interleukin-17 (IL-17)
- The researchers examined the global gene expression profiles in the mediastinal (pulmonary-draining) lymph nodes taken from both horses affected by RAO and control horses.
- They identified a differential expression of over 200 genes. This, along with network analysis, indicated an IL-17 response centered around a factor called NF-κB.
- Immunohistochemical analysis of the lymph node sections showed an increased staining intensity for IL-17 in diseased horses. This result, in combination with the finding of increased IL-17 concentrations in the lymph node homogenates from RAO-affected horses, supports the researchers’ theory of IL-17’s critical involvement in RAO.
Implications and Future Research
- Despite the significant findings, the actual source of the IL-17 molecule in this equine model of occupational asthma remains unknown. Therefore, further investigations are required to confirm the source of this molecule.
- The research implies that understanding the immune workings of RAO could lead to valuable insight into the development of future therapeutic interventions. This could benefit not only horses but also humans’ pulmonary health, particularly those affected by occupational asthma.
Cite This Article
APA
Korn A, Miller D, Dong L, Buckles EL, Wagner B, Ainsworth DM.
(2015).
Differential Gene Expression Profiles and Selected Cytokine Protein Analysis of Mediastinal Lymph Nodes of Horses with Chronic Recurrent Airway Obstruction (RAO) Support an Interleukin-17 Immune Response.
PLoS One, 10(11), e0142622.
https://doi.org/10.1371/journal.pone.0142622 Publication
Researcher Affiliations
- Department of Clinical Services, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
- Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
- Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
- Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
- Department of Clinical Services, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
MeSH Terms
- Airway Obstruction / genetics
- Airway Obstruction / metabolism
- Airway Obstruction / veterinary
- Animals
- Bronchoalveolar Lavage Fluid / cytology
- Chronic Disease
- Cytokines / genetics
- Cytokines / metabolism
- Female
- Horse Diseases / genetics
- Horse Diseases / metabolism
- Horses
- Immunohistochemistry
- Interleukin-17 / genetics
- Interleukin-17 / metabolism
- Interleukin-4 / genetics
- Interleukin-4 / metabolism
- Lymph Nodes / metabolism
- Male
- Mediastinum
- NF-kappa B / genetics
- NF-kappa B / metabolism
- Neutrophils / metabolism
- Oligonucleotide Array Sequence Analysis
- Recurrence
- Reverse Transcriptase Polymerase Chain Reaction
- Transcriptome
Conflict of Interest Statement
The authors have declared that no competing interests exist.
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