Correlation between Nuclear Factor- κ B Activity in Bronchial Brushing Samples and Lung Dysfunction in an Animal Model of Asthma

Abstract

Asthma is a chronic inflammatory disease of the airways, in which many inflammatory genes are overexpressed. Transcription factor, nuclear factor-kappaB (NF-kappaB), which is thought to control the transcriptional initiation of inflammatory genes, has been poorly investigated in asthma. In the present report, bronchial cells (BCs), recovered by bronchial brushing in healthy and heaves-affected horses (i.e., an animal model of asthma), were assessed for NF-kappaB activity. Small amounts of active NF-kappaB were present in BCs of healthy horses, whereas high levels of NF-kappaB activity was found during crisis (i.e., acute airway obstruction) in all heaves-affected horses. Three weeks after the crisis, the level of NF-kappaB activity found in BCs of heaves-affected horses was highly correlated (p < 0.01) to the degree of residual lung dysfunction. Unexpectedly, active NF- kappaB complexes found in BCs of heaves-affected horses were mainly p65 homodimers, rather than classic p65-p50 heterodimers. At last, intercellular adhesion molecule-1 (ICAM-1) expression paralleled p65 homodimers activity in these cells. These results demonstrate that the kinetics of NF-kappaB activity is strongly related to the course of the disease and confirm the relevance of NF-kappaB as a putative target in asthma therapy. Moreover, uncommon p65 homodimers could transactivate, in BCs, a subset of genes, such as ICAM-1, characteristic of chronic airway inflammation.

Early onset airway obstruction in response to organic dust in the horse

“…In addition, the airway inflammation may have partially resolved by 24 h as neutrophil infiltration into the pulmonary epithelial lining fluid occurs within 6 h of organic dust nebulization in RAO horses (29). Inhaled dust may induce the late-phase neutrophilic infiltration in RAO observed in the present study by enhancing the production of proinflammatory mediators from a range of cell types in addition to mast cells, such as alveolar macrophages, lymphocytes, and airway epithelial cells (6,7,24,41). Reduced numbers of macrophages and lymphocytes were evident in control horses immediately after challenge.…”

“…The late-phase response comprises airway obstruction, airway inflammation, and airway hyperreactivity. RAO has been suggested to be the most similar naturally occurring disease in animals to human asthma (35) and has been used as model of human asthma (2,6,17,39).…”

Rapid, Multiwell Colorimetric Assay for Measuring Neutrophil Chemoattractant Activity in Bronchoalveolar Lavage Fluid of Horses with Recurrent Airway Obstruction

“…2 Activity of NF-kB is increased in bronchial cells of RAO-affected horses and is highly correlated to the percentage of neutrophils present in the bronchi. 5,6 Selective blockage of NF-kB activity results in marked attenuation of allergic lung inflammation in antigen-sensitized mice. 9 On the basis of the results of the present study, whereby neutrophil chemoattractant activity in BALF was assessed with the MTT assay and found to be higher in RAO-affected horses compared with normal horses, this assay may be useful for monitoring the response to therapy of RAO-affected horses in future studies, regardless of the underlying chemoattractant.…”

Air Quality in Horse Stables

“…In the search for potential allergens involved in RAO, an intra-dermal skin test and serum IgE analysis have been evaluated, but these have not proven to be clinically reliable in horses (Lorch et al, 2001;Lebis et al, 2002). Bronchial brushings, BAL, tracheal lavage, exhaled breath condensate, and even lung tissue samples have been shown to be of value in the investigation of the inflammatory process in the equine lung (Bureau et al, 2000;Gerber et al, 2003;Wyse et al, 2005). Imaging techniques, such as radiographic examination of equine lung, however, have shown to be of little value for the diagnosis of lower grade inflammation (Mazan et al, 2005).…”