PloS one2015; 10(8); e0136103; doi: 10.1371/journal.pone.0136103

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

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.
Publication Date: 2015-08-20 PubMed ID: 26292153PubMed Central: PMC4546272DOI: 10.1371/journal.pone.0136103Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates how genes and pathways involved in a common lower airway disease in horses known as Recurrent Airway Obstruction (RAO), similar to human asthma, are affected. The study found significant differences in the expression profiles between RAO-affected horses and healthy ones predominantly upon exposure to hay dust extract. A notable discovery was the strong upregulation of CXCL13 and numerous genes involved in regulating the cell cycle in stimulated samples. Changes were also seen in the HIF-1 transcription factor target genes expression.

Investigation Methodology

  • The researchers performed an RNA-sequencing on peripheral blood mononuclear cells (PBMCs) of 40 RAO affected and 45 control horses from three cohorts of Warmblood horses.
  • These PBMCs were stimulated using several irritants, prominently hay dust extract.
  • Other stimulants included lipopolysaccharides and a recombinant parasite antigen.
  • The study maintained unstimulated samples for control comparison.
  • The total dataset for the study was made up of 561 individual samples.

Discovery of Differential Expression (DE)

  • Significant differences were noted in the expression profiles between RAO affected horses and the control ones upon stimulation with hay dust extract.
  • Key findings were the strong upregulation of CXCL13 and many cell cycle regulation genes in samples from RAO affected horses.
  • The expression of several HIF-1 transcription factor target genes in the RAO affected horses also saw changes.

Impact of RAO

  • The presence of RAO condition triggered systemic changes, mainly noticeable as differential expression profiles within the PBMCs of affected horses.
  • The changes also depended on the cohort and the stimulation of samples, dominated by genes involved in immune cell development, trafficking, and cell cycle regulation.

Significance of CXCL13 and CDC20

  • Upregulated gene CXCL13 and the cell cycle regulator CDC20 play an essential role in the immune response observed in RAO personally.
  • The prominence of CXCL13 is likely linked with its derivation from macrophages or Th17.

Cite This Article

APA
Pacholewska A, Jagannathan V, Dru00f6gemu00fcller M, Klukowska-Ru00f6tzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Leeb T, Gerber V. (2015). Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma. PLoS One, 10(8), e0136103. https://doi.org/10.1371/journal.pone.0136103

Publication

ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 10
Issue: 8
Pages: e0136103
PII: e0136103

Researcher Affiliations

Pacholewska, Alicja
  • Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland; Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Jagannathan, Vidhya
  • Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Dru00f6gemu00fcller, Michaela
  • Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Klukowska-Ru00f6tzler, Jolanta
  • Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland; Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Bern University Hospital, Bern, Switzerland.
Lanz, Simone
  • Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland.
Hamza, Eman
  • Clinical Immunology Group, Department of Clinical Research and Veterinary Public Health, University of Bern, Bern, Switzerland; Department of Zoonoses, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt.
Dermitzakis, Emmanouil T
  • Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Swiss Institute of Bioinformatics, Geneva, Switzerland.
Marti, Eliane
  • Clinical Immunology Group, Department of Clinical Research and Veterinary Public Health, University of Bern, Bern, Switzerland.
Leeb, Tosso
  • Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Gerber, Vincent
  • Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland.

MeSH Terms

  • Animals
  • Asthma / physiopathology
  • Asthma / veterinary
  • Case-Control Studies
  • Cell Cycle / physiology
  • Chemokine CXCL13 / metabolism
  • Female
  • Gene Expression Profiling / veterinary
  • Horse Diseases / physiopathology
  • Horses
  • Leukocytes, Mononuclear / physiology
  • Male
  • Models, Biological
  • Transcriptome

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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