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 inf lammatory gene expression, is increased in bronchial epithelial cells from horses suffering from heaves (a hypersensitivity-associated inflammatory co ndition 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 f or NF-KB activity. NF-KB activity was much higher in BAL cells from heaves- affected horses, especially during crisis (disease exacerbation), than in c ells from healthy horses. Moreover, the level of NF-KB activity found in BA L cells was positively correlated to total lung resistance and to the propo rtion of neutrophils present in BAL fluid. Finally, prototypical p65-p50 NF -KB heterodimers were absent from BAL cells, which mostly contained p65 hom odimers. These results (1) show that increased NF-kappaB activity is a gene ral feature of heaves lung; (2) demonstrate the importance of p65 homodimer s in neutrophilic inflammation; and (3) suggest that the use of specific NF -kappaB inhibitors could improve lung function in heaves-affected horses. ( C) 2001 Elsevier Science B.V All rights reserved.