title: 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.
authors.affiliation: Department of Veterinary Clinical Studies, Vetsuisse-Faculty University of Berne, Länggassstrasse 124, CH-3012 Bern, Switzerland. tryhner@gmx.ch
authors.forename: Thea
authors.initials: T
authors.lastname: Ryhner
authors.forename: N
authors.initials: N
authors.lastname: Müller
authors.forename: V
authors.initials: V
authors.lastname: Balmer
authors.forename: V
authors.initials: V
authors.lastname: Gerber
mesh_terms: D000402:Airway Obstruction / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D000818:Animals; D001784:Blood Gas Analysis / Q000662:veterinary; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D018118:Chloride Channels / Q000096:biosynthesis / Q000235:genetics; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006734:Horse Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D006736:Horses; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D055271:Mucin 5AC / Q000096:biosynthesis / Q000235:genetics; D009093:Mucus / Q000276:immunology / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary
chemical_list: D018118:Chloride Channels; D018793:Interleukin-13; D055271:Mucin 5AC; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D007371:Interferon-gamma; D066246:ErbB Receptors