title: 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.
authors.affiliation: Department of Clinical Services, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Korn
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Donald
authors.initials: D
authors.lastname: Miller
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Lynn
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Elizabeth Louise
authors.initials: EL
authors.lastname: Buckles
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Bettina
authors.initials: B
authors.lastname: Wagner
authors.affiliation: Department of Clinical Services, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Dorothy Marie
authors.initials: DM
authors.lastname: Ainsworth
mesh_terms: D000402:Airway Obstruction / Q000235:genetics* / Q000378:metabolism / Q000662:veterinary; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006734:Horse Diseases / Q000235:genetics* / Q000378:metabolism; D006736:Horses; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000235:genetics* / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism*; D008297:Male; D008482:Mediastinum; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D016328:NF-kappa B; D015847:Interleukin-4