Increased mucus accumulation in horses chronically affected with recurrent airway obstruction is not associated with up-regulation of CLCA1, EGFR, MUC5AC, Bcl-2, IL-13 and INF-gamma expression.
Abstract: The mechanisms leading to mucus accumulation in equine inflammatory airway disease (IAD) and recurrent airway obstruction (RAO) are unclear. In airways of human patients with asthma and/or chronic obstructive pulmonary disease as well as in animal models of these diseases, associations of mucus hyperproduction with increased calcium-activated chloride channel 1 (CLCA1), epidermal growth factor receptor (EGFR), mucin 5AC (MUC5AC), B-cell lymphoma 2 (Bcl-2), interleukin (IL)-13 and interferon (IFN)-gamma expression have been reported. We hypothesized that increased mucus accumulation in RAO and IAD are associated with alterations in inflammatory cytokine (IL-13 and IFN-gamma) and epithelial gene (CLCA1, EGFR, Bcl-2 and MUC5AC) profiles. Therefore, mRNA expression of these genes in cell pellets extracted from bronchoalveolar lavage fluid (BALF) and bronchial epithelial brushing (BEB) was compared between 11 clinically healthy (Control group), 7 IAD- and 12 RAO-affected horses by reverse transcription polymerase chain reaction. We also performed arterial blood gas analysis, endoscopic scoring of mucus accumulation in the trachea and cytology of tracheo-bronchial secretions (TBS) and of BALF. Tracheal mucus accumulation, along with TBS and BALF neutrophils were significantly increased and arterial pO(2) was decreased in RAO-affected horses compared to the Control group. IL-13 in BALF samples was significantly lower in the RAO group. None of the other genes' relative mRNA levels displayed significant differences between groups. Our findings suggest that mucus production in equine RAO is induced by pathways independent of IL-13, CLCA1, EGFR, MUC5AC and Bcl-2 up-regulation.
Publication Date: 2008-05-23 PubMed ID: 18597857DOI: 10.1016/j.vetimm.2008.05.011Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Asthma
- Bronchi
- Bronchoalveolar Lavage
- Chronic Obstructive Pulmonary Disease
- Clinical Study
- Cytokines
- Diagnosis
- Disease Diagnosis
- Disease Etiology
- Equine Diseases
- Equine Health
- Horses
- Inflammation
- Inflammatory Response
- Interleukins
- Molecular biology
- Neutrophils
- Recurrent Airway Obstruction
- Respiratory Disease
- Trachea
- Veterinary Medicine
Summary
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This research article investigates the mechanisms of mucus accumulation in horses suffering from Inflammatory Airway Disease (IAD) and Recurrent Airway Obstruction (RAO). Contrary to prior beliefs, findings reveal that this condition is not linked to up-regulation of certain genes and inflammatory cytokines commonly associated with similar diseases in humans.
Background
- Mucus build-up is a common issue in horses with inflammatory airway disease (IAD) and recurrent airway obstruction (RAO), but the reasons behind this aren’t fully understood.
- In humans and animal models with asthma or chronic obstructive pulmonary disease (COPD), mucus overproduction has been associated with increased expression of specific genes and cytokines, including CLCA1, EGFR, MUC5AC, Bcl-2, IL-13, and INF-gamma.
- The researchers hypothesized a similar association might exist for horses suffering from IAD and RAO.
Methodology
- The research team compared mRNA expression of the above-mentioned genes in cell samples obtained from bronchoalveolar lavage fluid and bronchial epithelial brushing in healthy horses and those affected by IAD and RAO.
- The comparison involved 11 healthy horses, 7 afflicted by IAD, and 12 suffering from RAO.
- Several tests were performed, including arterial blood gas analysis, endoscopic scoring of mucus accumulation, and cytology of tracheo-bronchial secretions and BALF.
Findings
- Results indicated that mucus build-up, along with tracheo-bronchial secretions and BALF neutrophils, were significantly higher in horses with RAO than in the control group. Additionally, arterial pO(2) was found to be lower in the RAO group.
- Interestingly, IL-13 levels in BALF samples were markedly lower in the RAO disease group.
- The mRNA levels for the other studied genes showed no significant variation between the groups, refuting the initial hypothesis and suggesting other mechanisms at play.
Conclusion
- The study concludes that, unlike in humans with asthma or COPD, mucus overproduction in equine RAO is not caused by the up-regulation of the genes CLCA1, EGFR, MUC5AC, and Bcl-2, or the inflammatory cytokines IL-13 and INF-gamma.
- This finding indicates that distinct pathways may be involved in inducing mucus production in horses with this condition, opening new avenues for research and treatment.
Cite This Article
APA
Ryhner T, Müller N, Balmer V, Gerber V.
(2008).
Increased mucus accumulation in horses chronically affected with recurrent airway obstruction is not associated with up-regulation of CLCA1, EGFR, MUC5AC, Bcl-2, IL-13 and INF-gamma expression.
Vet Immunol Immunopathol, 125(1-2), 8-17.
https://doi.org/10.1016/j.vetimm.2008.05.011 Publication
Researcher Affiliations
- Department of Veterinary Clinical Studies, Vetsuisse-Faculty University of Berne, Länggassstrasse 124, CH-3012 Bern, Switzerland. tryhner@gmx.ch
MeSH Terms
- Airway Obstruction / genetics
- Airway Obstruction / immunology
- Airway Obstruction / pathology
- Airway Obstruction / veterinary
- Animals
- Blood Gas Analysis / veterinary
- Bronchoalveolar Lavage Fluid / chemistry
- Bronchoalveolar Lavage Fluid / cytology
- Cell Count
- Chloride Channels / biosynthesis
- Chloride Channels / genetics
- ErbB Receptors / biosynthesis
- ErbB Receptors / genetics
- Female
- Horse Diseases / genetics
- Horse Diseases / immunology
- Horse Diseases / pathology
- Horses
- Interferon-gamma / biosynthesis
- Interleukin-13 / biosynthesis
- Interleukin-13 / genetics
- Male
- Mucin 5AC / biosynthesis
- Mucin 5AC / genetics
- Mucus / immunology
- Mucus / metabolism
- Proto-Oncogene Proteins c-bcl-2 / biosynthesis
- Proto-Oncogene Proteins c-bcl-2 / genetics
- RNA, Messenger / biosynthesis
- RNA, Messenger / genetics
- Reverse Transcriptase Polymerase Chain Reaction / veterinary
Citations
This article has been cited 4 times.- Couëtil LL, Cardwell JM, Gerber V, Lavoie JP, Léguillette R, Richard EA. Inflammatory Airway Disease of Horses--Revised Consensus Statement.. J Vet Intern Med 2016 Mar-Apr;30(2):503-15.
- Richard EA, Depecker M, Defontis M, Leleu C, Fortier G, Pitel PH, Couroucé-Malblanc A. Cytokine concentrations in bronchoalveolar lavage fluid from horses with neutrophilic inflammatory airway disease.. J Vet Intern Med 2014 Nov-Dec;28(6):1838-44.
- Rousseau K, Cardwell JM, Humphrey E, Newton R, Knight D, Clegg P, Thornton DJ. Muc5b is the major polymeric mucin in mucus from thoroughbred horses with and without airway mucus accumulation.. PLoS One 2011;6(5):e19678.
- Schwab UE, Fulcher ML, Randell SH, Flaminio MJ, Russell DG. Equine bronchial epithelial cells differentiate into ciliated and mucus producing cells in vitro.. In Vitro Cell Dev Biol Anim 2010 Feb;46(2):102-6.
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