Correlation between nuclear factor-kappaB 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.
Publication Date: 2000-04-14 PubMed ID: 10764329DOI: 10.1164/ajrccm.161.4.9907010Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research study investigates the link between nuclear factor-kappaB (NF-kappaB) activity in bronchial brushing samples and lung dysfunction in an asthma model using horses. The findings suggest that the increase in NF-kappaB, notably p65 homodimers, observed in horses with respiratory distress is strongly associated with the progression of asthma, offering potential therapeutic targets for the disease.
Understanding Asthma and NF-kappaB
- Asthma is a chronic disease characterized by inflammation of the airways, leading to an overexpression of inflammatory genes. One such gene is controlled by a transcription factor known as nuclear factor-kappaB (NF-kappaB), which, despite its essential role, has not been thoroughly explored in the context of asthma.
NF-kappaB activity in Healthy vs. Asthmatic Horses
- This research assessed the activity of NF-kappaB in bronchial cells (BCs) recovered through bronchial brushing from healthy horses and those suffering from heaves, an asthma-like condition.
- The researchers found small amounts of active NF-kappaB in the BCs of healthy horses. In contrast, high levels of NF-kappaB activity were observed during acute airway obstruction episodes in all of the heaves-affected horses.
Correlation between lung dysfunction and NF-kappaB activity level
- Three weeks after the airway obstruction crises, the NF-kappaB activity levels found in BCs of heaves-affected horses were highly related to the degree of residual lung dysfunction.
Characteristics of NF-kappaB in Asthmatic Horses
- The active NF-kappaB complexes observed in BCs of heaves-affected horses were primarily p65 homodimers, a form different from the classic p65-p50 heterodimers usually found.
- This uncommon form, p65 homodimers, seem to be able to activate a subset of genes, including the intercellular adhesion molecule-1 (ICAM-1). The expression of ICAM-1 parallels the activity of p65 homodimers in these cells, which is characteristic of chronic airway inflammation associated with asthma.
Implications for Asthma Therapy
- The strong relationship between the progression of the disease and the kinetic activity of NF-kappaB demonstrates its potential as a target in asthma therapy.
- The unique form of active NF-kappaB observed in the study (p65 homodimers) brings new perspectives to the biological understanding of asthma and the development of novel therapeutic strategies.
Cite This Article
APA
Bureau F, Bonizzi G, Kirschvink N, Delhalle S, Desmecht D, Merville MP, Bours V, Lekeux P.
(2000).
Correlation between nuclear factor-kappaB activity in bronchial brushing samples and lung dysfunction in an animal model of asthma.
Am J Respir Crit Care Med, 161(4 Pt 1), 1314-1321.
https://doi.org/10.1164/ajrccm.161.4.9907010 Publication
Researcher Affiliations
- Department of Physiology, Faculty of Veterinary Medicine, and Laboratory of Medical Chemistry, Faculty of Medicine, University of Liu00e8ge, Liu00e8ge, Belgium. fabrice.bureau@ulg.ac.be
MeSH Terms
- Animals
- Asthma / physiopathology
- Bronchi / metabolism
- Bronchi / pathology
- Disease Models, Animal
- Horse Diseases / physiopathology
- Horses / physiology
- Immunoblotting
- Intercellular Adhesion Molecule-1 / metabolism
- Lung / physiopathology
- Lung Diseases, Obstructive / physiopathology
- Lung Diseases, Obstructive / veterinary
- NF-kappa B / metabolism
Citations
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