Correlation between nuclear factor-kappa B activity in bronchial brushing samples and lung dysfunction in an animal model of asthma

Asthma is a chronic inflammatory disease of the airways, in which many infl ammatory genes are overexpressed. Transcription factor, nuclear factor-kapp a B (NF-kappa B), which is thought to control the transcriptional initiatio n of inflammatory genes, has been poorly investigated in asthma. In the pre sent report, bronchial cells (BCs), recovered by bronchial brushing in heal thy and heaves-affected horses (i.e., an animal model of asthma), were asse ssed for NF-kappa B activity. Small amounts of active NF-kappa B were prese nt in BCs of healthy horses, whereas high levels of NF-kappa B activity was found during crisis (i.e, acute airway obstruction) in all heaves-affected horses. Three weeks after the crisis, the level of NF-kappa B activity fou nd in BCs of heaves-affected horses was highly correlated (p < 0.01) to the degree of residual lung dysfunction. Unexpectedly, active NF-kappa B compl exes found in BCs of heaves-affected horses were mainly p65 homodimers, rat her than classic p65-p50 heterodimers. At last, intercellular adhesion mole cule-1 (ICAM-1) expression paralleled p65 homodimers activity in these cell s. These results demonstrate that the kinetics of NF-kappa B activity is st rongly related to the course of the disease and confirm the relevance of NF -kappa B as a putative target in asthma therapy. Moreover, uncommon p65 hom odimers could transactivate, in BCs, a subset of genes, such as ICAM-1, cha racteristic of chronic airway inflammation.