DNA binding activity of transcription factors in bronchial cells of horses with recurrent airway obstruction.
Abstract: Horses with recurrent airway obstruction (RAO) present many similarities with human asthmatics including airway inflammation, hyperresponsiveness, reversible obstruction, and increased NF-kappaB expression. Studies in experimental asthma models have shown that transcriptions factors such as activator protein-1 (AP-1), GATA-3, cyclic AMP response element binding protein (CREB) and CAAT/enhancer binding protein (C/EBP) may also play an important role in airway inflammation. The purpose of this study was to measure DNA binding activity of these transcription factors in the airways of horses with RAO and to compare it to pulmonary function and bronchoalveolar lavage fluid (BALF) cytology. Seven horses with RAO and six control animals were studied during a moldy hay challenge and after 2 months at pasture. Pulmonary function, BALF cytology and transcription factors' activities in bronchial brushings were measured during hay and pasture exposures. During moldy hay challenge, RAO-affected horses developed severe airway obstruction and inflammation and a significantly higher airway AP-1 binding activity than in controls. After 2 months on pasture, pulmonary function and airway AP-1 binding activity were not different between RAO and control horses. The DNA binding activity of CREB in airways of RAO-affected horses increased significantly after 2 months at pasture and became higher than in controls. A significant positive correlation was detected between AP-1 binding activity and indicators of airway obstruction and inflammation. Airway GATA-3, CEBP and CREB binding activities were negatively correlated with indices of airway obstruction. However, contrarily to CREB binding activity, GATA-3 and CEBP binding activities were not different between RAO and control horses and were unaffected by changes in environment. These data support the view that AP-1 and CREB play a role in modulating airway inflammation in horses with RAO.
Publication Date: 2006-06-05 PubMed ID: 16753225DOI: 10.1016/j.vetimm.2006.03.020Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The researchers studied the role of certain transcription factors in horses with recurrent airway obstruction (RAO) and found out their DNA binding activities were different during airway obstruction and inflammation.
Objective and Methodology
- The goal of this research was to examine the DNA binding activity of certain transcription factors in the airways of horses suffering from RAO and compare it to pulmonary function and bronchoalveolar lavage fluid (BALF) cytology.
- The study involved seven horses with RAO and six control animals. They were observed during a moldy hay challenge and after 2 months at pasture.
- The researchers measured pulmonary function, BALF cytology, and the activities of transcription factors in bronchial brushings during hay and pasture exposures.
Results and Findings
- During the moldy hay challenge, RAO-affected horses developed severe airway obstruction and inflammation. Their airways also had a significantly higher activity of the AP-1 transcription factor compared to the controls.
- After 2 months at pasture, both pulmonary function and airway AP-1 binding activity weren’t different between RAO horses and controls.
- The DNA binding activity of the transcription factor CREB in airways of RAO-affected horses significantly increased after 2 months at pasture and became higher than in controls.
- The study found a positive correlation between AP-1 binding activity and indicators of airway obstruction and inflammation.
- Airway activities of GATA-3, CEBP and CREB transcription factors were negatively correlated with indices of airway obstruction. However, GATA-3 and CEBP binding activities weren’t different between RAO and control horses, and they were unaffected by changes in the environment unlike CREB binding activity.
Conclusion
- The results of this study provide support to the idea that transcription factors AP-1 and CREB play an important role in modulating airway inflammation in horses suffering from RAO.
Cite This Article
APA
Couëtil LL, Art T, de Moffarts B, Becker M, Mélotte D, Jaspar F, Bureau F, Lekeux P.
(2006).
DNA binding activity of transcription factors in bronchial cells of horses with recurrent airway obstruction.
Vet Immunol Immunopathol, 113(1-2), 11-20.
https://doi.org/10.1016/j.vetimm.2006.03.020 Publication
Researcher Affiliations
- Department of Physiology, Faculty of Veterinary Medicine, University of Liège, Bat B42, Liège B-4000, Belgium. couetill@purdue.edu
MeSH Terms
- Animals
- Binding, Competitive
- Bronchoalveolar Lavage Fluid / cytology
- CCAAT-Enhancer-Binding Proteins / metabolism
- CREB-Binding Protein / metabolism
- DNA / metabolism
- Disease Models, Animal
- Electrophoretic Mobility Shift Assay / veterinary
- Female
- GATA3 Transcription Factor / metabolism
- Horse Diseases / genetics
- Horse Diseases / metabolism
- Horses
- Lung Diseases, Obstructive / genetics
- Lung Diseases, Obstructive / metabolism
- Lung Diseases, Obstructive / veterinary
- Male
- Respiratory Function Tests / veterinary
- Respiratory Hypersensitivity / genetics
- Respiratory Hypersensitivity / metabolism
- Respiratory Hypersensitivity / veterinary
- Transcription Factor AP-1 / metabolism
- Transcription Factors / metabolism
Citations
This article has been cited 7 times.- Olave CJ, Ivester KM, Couetil LL, Burgess J, Park JH, Mukhopadhyay A. Effects of low-dust forages on dust exposure, airway cytology, and plasma omega-3 concentrations in Thoroughbred racehorses: A randomized clinical trial. J Vet Intern Med 2023 Jan;37(1):338-348.
- Klier J, Bartl C, Geuder S, Geh KJ, Reese S, Goehring LS, Winter G, Gehlen H. Immunomodulatory asthma therapy in the equine animal model: A dose-response study and evaluation of a long-term effect. Immun Inflamm Dis 2019 Sep;7(3):130-149.
- Tessier L, Côté O, Clark ME, Viel L, Diaz-Méndez A, Anders S, Bienzle D. Gene set enrichment analysis of the bronchial epithelium implicates contribution of cell cycle and tissue repair processes in equine asthma. Sci Rep 2018 Nov 6;8(1):16408.
- Bartel S, Schulz N, Alessandrini F, Schamberger AC, Pagel P, Theis FJ, Milger K, Noessner E, Stick SM, Kicic A, Eickelberg O, Freishtat RJ, Krauss-Etschmann S. Pulmonary microRNA profiles identify involvement of Creb1 and Sec14l3 in bronchial epithelial changes in allergic asthma. Sci Rep 2017 Apr 6;7:46026.
- Moran G, Folch H, Henriquez C, Ortloff A, Barria M. Reaginic antibodies from horses with recurrent airway obstruction produce mast cell stimulation. Vet Res Commun 2012 Dec;36(4):251-8.
- Riihimäki M, Raine A, Pourazar J, Sandström T, Art T, Lekeux P, Couëtil L, Pringle J. Epithelial expression of mRNA and protein for IL-6, IL-10 and TNF-alpha in endobronchial biopsies in horses with recurrent airway obstruction. BMC Vet Res 2008 Feb 23;4:8.
- Simões J, Tilley P. Decision Making in Severe Equine Asthma-Diagnosis and Monitoring. Animals (Basel) 2023 Dec 16;13(24).
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