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Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.

Pacholewska A, Jagannathan V, Drögemüller M, Klukowska-Rötzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Leeb T, Gerber V - PLoS ONE (2015)

Bottom Line: The RAO condition alters systemic changes observed as differential expression profiles of PBMCs.Those changes also depended on the cohort and stimulation of the samples and were dominated by genes involved in immune cell trafficking, development, and cell cycle regulation.Our findings indicate an important role of CXCL13, likely macrophage or Th17 derived, and the cell cycle regulator CDC20 in the immune response in RAO.

View Article: PubMed Central - PubMed

Affiliation: Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland; Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

ABSTRACT
Recurrent airway obstruction (RAO) is a common and potentially debilitating lower airway disease in horses, which shares many similarities with human asthma. In susceptible horses RAO exacerbation is caused by environmental allergens and irritants present in hay dust. The objective of this study was the identification of genes and pathways involved in the pathology of RAO by global transcriptome analyses in stimulated peripheral blood mononuclear cells (PBMCs). We performed RNA-seq on PBMCs derived from 40 RAO affected and 45 control horses belonging to three cohorts of Warmblood horses: two half-sib families and one group of unrelated horses. PBMCs were stimulated with hay dust extract, lipopolysaccharides, a recombinant parasite antigen, or left unstimulated. The total dataset consisted of 561 individual samples. We detected significant differences in the expression profiles between RAO and control horses. Differential expression (DE) was most marked upon stimulation with hay dust extract. An important novel finding was a strong upregulation of CXCL13 together with many genes involved in cell cycle regulation in stimulated samples from RAO affected horses, in addition to changes in the expression of several HIF-1 transcription factor target genes. The RAO condition alters systemic changes observed as differential expression profiles of PBMCs. Those changes also depended on the cohort and stimulation of the samples and were dominated by genes involved in immune cell trafficking, development, and cell cycle regulation. Our findings indicate an important role of CXCL13, likely macrophage or Th17 derived, and the cell cycle regulator CDC20 in the immune response in RAO.

No MeSH data available.


Related in: MedlinePlus

Biological processes enriched by RAO-regulated genes.The bars represent the number of RAO-regulated genes by the overall RAO-effect, regardless stimulation and/or cohort.
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pone.0136103.g004: Biological processes enriched by RAO-regulated genes.The bars represent the number of RAO-regulated genes by the overall RAO-effect, regardless stimulation and/or cohort.

Mentions: The RAO regulated genes comprised of genes involved in e.g. immune response, cell differentiation, and response to hypoxia as shown in Fig 4.


Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.

Pacholewska A, Jagannathan V, Drögemüller M, Klukowska-Rötzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Leeb T, Gerber V - PLoS ONE (2015)

Biological processes enriched by RAO-regulated genes.The bars represent the number of RAO-regulated genes by the overall RAO-effect, regardless stimulation and/or cohort.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4546272&req=5

pone.0136103.g004: Biological processes enriched by RAO-regulated genes.The bars represent the number of RAO-regulated genes by the overall RAO-effect, regardless stimulation and/or cohort.
Mentions: The RAO regulated genes comprised of genes involved in e.g. immune response, cell differentiation, and response to hypoxia as shown in Fig 4.

Bottom Line: The RAO condition alters systemic changes observed as differential expression profiles of PBMCs.Those changes also depended on the cohort and stimulation of the samples and were dominated by genes involved in immune cell trafficking, development, and cell cycle regulation.Our findings indicate an important role of CXCL13, likely macrophage or Th17 derived, and the cell cycle regulator CDC20 in the immune response in RAO.

View Article: PubMed Central - PubMed

Affiliation: Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland; Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

ABSTRACT
Recurrent airway obstruction (RAO) is a common and potentially debilitating lower airway disease in horses, which shares many similarities with human asthma. In susceptible horses RAO exacerbation is caused by environmental allergens and irritants present in hay dust. The objective of this study was the identification of genes and pathways involved in the pathology of RAO by global transcriptome analyses in stimulated peripheral blood mononuclear cells (PBMCs). We performed RNA-seq on PBMCs derived from 40 RAO affected and 45 control horses belonging to three cohorts of Warmblood horses: two half-sib families and one group of unrelated horses. PBMCs were stimulated with hay dust extract, lipopolysaccharides, a recombinant parasite antigen, or left unstimulated. The total dataset consisted of 561 individual samples. We detected significant differences in the expression profiles between RAO and control horses. Differential expression (DE) was most marked upon stimulation with hay dust extract. An important novel finding was a strong upregulation of CXCL13 together with many genes involved in cell cycle regulation in stimulated samples from RAO affected horses, in addition to changes in the expression of several HIF-1 transcription factor target genes. The RAO condition alters systemic changes observed as differential expression profiles of PBMCs. Those changes also depended on the cohort and stimulation of the samples and were dominated by genes involved in immune cell trafficking, development, and cell cycle regulation. Our findings indicate an important role of CXCL13, likely macrophage or Th17 derived, and the cell cycle regulator CDC20 in the immune response in RAO.

No MeSH data available.


Related in: MedlinePlus