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

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.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.Recurrent airway obstruction (RAO) or heaves is a well-known respiratory disease in horses that shares any pathophysiological similarities with asthma in humans [1-3]. RAO is a severe, potentially debilitating, chronic inflammatory airway disease typically affecting middle-aged horses. Acute exacerbations are characterized by neutrophilic airway inflammation, coughing, periods of labored breathing at rest and exercise intolerance due to bronchospasm and mucus accumulation in the airways [4]. It is initiated following exposure to organic dusts, molds, and lipopolysaccharides (LPS) in hay [5]. Periods of acute exacerbation are interspersed by periods of remission, when horses are kept away from the causative environment [3]. The immunological processes responsible for the persistent airway inflammation are still largely unknown [6]. RAO is thought to result from an aberrant immune response orchestrated by antigen-specific T lymphocytes via the secretion of pro-inflammatory cytokines. Whether these T lymphocytes have a type 1 or type 2 phenotype and cytokine secretion profile is still a m