Impaired response of the bronchial epithelium to inflammation characterizes severe equine asthma

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Tessier , L , Cote , O , Clark , M E , Viel , L , Diaz-Mendez , A , Anders , S & Bienzle , D 2017 , ' Impaired response of the bronchial epithelium to inflammation characterizes severe equine asthma ' , BMC Genomics , vol. 18 , 708 .

Title: Impaired response of the bronchial epithelium to inflammation characterizes severe equine asthma
Author: Tessier, Laurence; Cote, Olivier; Clark, Mary Ellen; Viel, Laurent; Diaz-Mendez, Andres; Anders, Simon; Bienzle, Dorothee
Contributor organization: Institute for Molecular Medicine Finland
University of Helsinki
Date: 2017-09-08
Language: eng
Number of pages: 21
Belongs to series: BMC Genomics
ISSN: 1471-2164
Abstract: Background: Severe equine asthma is a naturally occurring lung inflammatory disease of mature animals characterized by neutrophilic inflammation, bronchoconstriction, mucus hypersecretion and airway remodeling. Exacerbations are triggered by inhalation of dust and microbial components. Affected animals eventually are unable of aerobic performance. In this study transcriptomic differences between asthmatic and non-asthmatic animals in the response of the bronchial epithelium to an inhaled challenge were determined. Results: Paired endobronchial biopsies were obtained pre- and post-challenge from asthmatic and non-asthmatic animals. The transcriptome, determined by RNA-seq and analyzed with edgeR, contained 111 genes differentially expressed (DE) after challenge between horses with and without asthma, and 81 of these were upregulated. Genes involved in neutrophil migration and activation were in central location in interaction networks, and related gene ontology terms were significantly overrepresented. Relative abundance of specific gene products as determined by immunohistochemistry was correlated with differential gene expression. Gene sets involved in neutrophil chemotaxis, immune and inflammatory response, secretion, blood coagulation and apoptosis were overrepresented among up-regulated genes, while the rhythmic process gene set was overrepresented among down-regulated genes. MMP1, IL8, TLR4 and MMP9 appeared to be the most important proteins in connecting the STRING protein network of DE genes. Conclusions: Several differentially expressed genes and networks in horses with asthma also contribute to human asthma, highlighting similarities between severe human adult and equine asthma. Neutrophil activation by the bronchial epithelium is suggested as the trigger of the inflammatory cascade in equine asthma, followed by epithelial injury and impaired repair and differentiation. Circadian rhythm dysregulation and the sonic Hedgehog pathway were identified as potential novel contributory factors in equine asthma.
Subject: Asthma
Differential expression analysis
High-throughput nucleotide sequencing
3111 Biomedicine
1184 Genetics, developmental biology, physiology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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