P65 Homodimer Activity in Distal Airway Cells Determines Lung Dysfunction in Equine Heaves

Nuclear factor-kappaB (NF-kappaB) 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-kappaB activity. NF-kappaB 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-kappaB 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-kappaB heterodimers were absent from BAL cells, which mostly contained p65 homodimers. These results (1) show that increased NF-kappaB 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-kappaB inhibitors could improve lung function in heaves-affected horses.