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.
Sandersen
C
C
Department of Physiology, Faculty of Veterinary Medicine, University of Liège, Bât. B42, Sart Tilman, B-4000 Liège, Belgium.
Bureau
F
F
Turlej
R
R
Fiévez
L
L
Dogné
S
S
Kirschvink
N
N
Lekeux
P
P
D000818:Animals; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D015342:DNA Probes / Q000235:genetics; D019281:Dimerization; D006734:Horse Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006736:Horses; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000473:pathology; D012140:Respiratory Tract Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D051996:Transcription Factor RelA
D015342:DNA Probes; D016328:NF-kappa B; D051996:Transcription Factor RelA