p65 Homodimer activity in distal airway cells determines lung dysfunction in equine heaves |
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| Authors: | C Sandersen F Bureau R Turlej L Fivez S Dogn N Kirschvink P Lekeux |
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| Institution: | Department of Physiology, Faculty of Veterinary Medicine, University of Liège, Bât. B42, Sart Tilman, B-4000 Liège, Belgium |
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| Abstract: | Nuclear factor-κB (NF-κB) activity, which is a key regulator of inflammatory gene expression, is increased in bronchial epithelial cells from horses suffering from heaves (a hypersensitivity-associated inflammatory condition of the lung). To determine whether this increased activity extends to distal airways and to other pulmonary cells, cells recovered by broncho-alveolar lavage (BAL) in healthy and heaves-affected horses were assessed for NF-κB activity. NF-κB activity was much higher in BAL cells from heaves-affected horses, especially during crisis (disease exacerbation), than in cells from healthy horses. Moreover, the level of NF-κB activity found in BAL cells was positively correlated to total lung resistance and to the proportion of neutrophils present in BAL fluid. Finally, prototypical p65–p50 NF-κB heterodimers were absent from BAL cells, which mostly contained p65 homodimers. These results (1) show that increased NF-κB activity is a general feature of heaves lung; (2) demonstrate the importance of p65 homodimers in neutrophilic inflammation; and (3) suggest that the use of specific NF-κB inhibitors could improve lung function in heaves-affected horses. |
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| Keywords: | Nuclear factor-κB Lung resistance Inflammation Neutrophils |
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