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BMC veterinary research2012; 8; 64; doi: 10.1186/1746-6148-8-64

Increased hypoxia-inducible factor 1α expression in lung cells of horses with recurrent airway obstruction.

Abstract: Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological processes responsible for the development and the persistence of airway inflammation are still largely unknown. Hypoxia-inducible factor (Hif) is mainly known as a major regulator of energy homeostasis and cellular adaptation to hypoxia. More recently however, Hif also emerged as an essential regulator of innate immune responses. Here, we aimed at investigating the potential involvement of Hif1-α in myeloid cells in horse with recurrent airway obstruction. Results: In vitro, we observed that Hif is expressed in equine myeloid cells after hay dust stimulation and regulates genes such as tumor necrosis factor alpha (TNF-α), interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGF-A). We further showed in vivo that airway challenge with hay dust upregulated Hif1-α mRNA expression in myeloid cells from the bronchoalveolar lavage fluid (BALF) of healthy and RAO-affected horses, with a more pronounced effect in cells from RAO-affected horses. Finally, Hif1-α mRNA expression in BALF cells from challenged horses correlated positively with lung dysfunction. Conclusions: Taken together, our results suggest an important role for Hif1-α in myeloid cells during hay dust-induced inflammation in horses with RAO. We therefore propose that future research aiming at functional inactivation of Hif1 in lung myeloid cells could open new therapeutic perspectives for RAO.
Publication Date: 2012-05-23 PubMed ID: 22621400PubMed Central: PMC3536633DOI: 10.1186/1746-6148-8-64Google Scholar: Lookup
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  • Journal Article

Summary

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The study reveals a possible link between increased Hypoxia-inducible factor 1α (Hif1-α) expression in lung cells and recurrent airway obstruction (RAO) in horses. The research showed that Hif has an important role in the inflammation caused by hay dust in horses suffering from RAO.

Research Objectives and Background

  • The study aimed to investigate the role of Hypoxia-inducible factor 1α (Hif1-α) in equine myeloid cells during Recurrent Airway Obstruction (RAO), an inflammatory condition in horses that results from exposure to organic dusts in hay.
  • Previously, Hif had been recognized as a vital regulator of energy homeostasis and cellular adaptation to hypoxia. However, recent studies show that Hif also regulates innate immune responses, indicating a possible role in the development and persistence of airway inflammation in RAO.

Methodology and Results

  • The study involved in vitro observation where researchers noted that Hif expression occurs in equine myeloid cells when stimulated by hay dust. This Hif expression also regulated genes like tumor necrosis factor alpha (TNF-α), interleukin-8 (IL-8), and vascular endothelial growth factor A (VEGF-A).
  • Through in vivo studies, the study found that a challenge with hay dust upregulated Hif1-α mRNA expression in myeloid cells from bronchoalveolar lavage fluid (BALF). The effect was more significant in cells from RAO-affected horses.
  • The study observed a positive correlation between Hif1-α mRNA expression in BALF cells from dust-challenged horses and lung dysfunction, hinting at Hif1-α’s crucial role in the hay dust-induced inflammation in RAO horses.

Conclusions and Future Directions

  • The study concluded that the Hif1-α in myeloid cells has a significant role in hay dust-induced inflammation seen in horses with RAO.
  • As a result of these findings, the study proposes further research to explore the option of functionally inactivating Hif1 in lung myeloid cells, which could open new therapeutic avenues for treating RAO.

Cite This Article

APA
Toussaint M, Fievez L, Desmet CJ, Pirottin D, Farnir F, Bureau F, Lekeux P. (2012). Increased hypoxia-inducible factor 1α expression in lung cells of horses with recurrent airway obstruction. BMC Vet Res, 8, 64. https://doi.org/10.1186/1746-6148-8-64

Publication

ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 8
Pages: 64

Researcher Affiliations

Toussaint, Marie
  • Laboratory of Cellular and Molecular Physiology, GIGA-Research and Faculty of Veterinary Medicine, University of Liège, B34-Avenue de l'Hôpital, 1, 4000, Liège, Belgium. M.Toussaint@ulg.ac.be
Fievez, Laurence
    Desmet, Christophe J
      Pirottin, Dimitri
        Farnir, Frédéric
          Bureau, Fabrice
            Lekeux, Pierre

              MeSH Terms

              • Animals
              • Antitussive Agents / pharmacology
              • Cells, Cultured
              • Dust
              • Gene Expression Regulation / physiology
              • Horse Diseases / metabolism
              • Horses
              • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
              • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
              • Inflammation / metabolism
              • Inflammation / veterinary
              • Interleukin-8 / genetics
              • Interleukin-8 / metabolism
              • Lung / cytology
              • Lung / metabolism
              • Lung Diseases, Obstructive / metabolism
              • Lung Diseases, Obstructive / veterinary
              • Monocytes / drug effects
              • Monocytes / metabolism
              • Noscapine / pharmacology
              • RNA, Messenger / genetics
              • RNA, Messenger / metabolism
              • Tumor Necrosis Factor-alpha / genetics
              • Tumor Necrosis Factor-alpha / metabolism
              • Vascular Endothelial Growth Factor A / genetics
              • Vascular Endothelial Growth Factor A / metabolism

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