FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
American journal of respiratory and critical care medicine2000; 161(4 Pt 1); 1314-1321; doi: 10.1164/ajrccm.161.4.9907010

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.
Get Full Text
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.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

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

American journal of respiratory and critical care medicine
ISSN: 1073-449X
NlmUniqueID: 9421642
Country: United States
Language: English
Volume: 161
Issue: 4 Pt 1
Pages: 1314-1321

Researcher Affiliations

Bureau, F
  • Department of Physiology, Faculty of Veterinary Medicine, and Laboratory of Medical Chemistry, Faculty of Medicine, University of Liège, Liège, Belgium. fabrice.bureau@ulg.ac.be
Bonizzi, G
    Kirschvink, N
      Delhalle, S
        Desmecht, D
          Merville, M P
            Bours, V
              Lekeux, P

                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

                This article has been cited 23 times.
                1. Rutledge JJ, Paegelow J, Ritchey J, Singh A, Rizzi T, Murray C, Gilliam L, Crisman E, Williams NJ, Holbrook TC. Nebulized glycosylated caffeic acid phenylether ester attenuation of environmental particulate-induced airway inflammation in horses. Front Vet Sci 2022;9:958567.
                  doi: 10.3389/fvets.2022.958567pubmed: 36406065google scholar: lookup
                2. Lee GKC, Beeler-Marfisi J, Viel L, Piché É, Kang H, Sears W, Bienzle D. Bronchial brush cytology, endobronchial biopsy, and SALSA immunohistochemistry in severe equine asthma. Vet Pathol 2022 Jan;59(1):100-111.
                  doi: 10.1177/03009858211048635pubmed: 34903109google scholar: lookup
                3. Mainguy-Seers S, Lavoie JP. Glucocorticoid treatment in horses with asthma: A narrative review. J Vet Intern Med 2021 Jul;35(4):2045-2057.
                  doi: 10.1111/jvim.16189pubmed: 34085342google scholar: lookup
                4. Hulliger MF, Pacholewska A, Vargas A, Lavoie JP, Leeb T, Gerber V, Jagannathan V. An Integrative miRNA-mRNA Expression Analysis Reveals Striking Transcriptomic Similarities between Severe Equine Asthma and Specific Asthma Endotypes in Humans. Genes (Basel) 2020 Sep 28;11(10).
                  doi: 10.3390/genes11101143pubmed: 32998415google scholar: lookup
                5. Couetil L, Cardwell JM, Leguillette R, Mazan M, Richard E, Bienzle D, Bullone M, Gerber V, Ivester K, Lavoie JP, Martin J, Moran G, Niedźwiedź A, Pusterla N, Swiderski C. Equine Asthma: Current Understanding and Future Directions. Front Vet Sci 2020;7:450.
                  doi: 10.3389/fvets.2020.00450pubmed: 32903600google scholar: lookup
                6. Tessier L, Côté O, Clark ME, Viel L, Diaz-Méndez A, Anders S, Bienzle D. Gene set enrichment analysis of the bronchial epithelium implicates contribution of cell cycle and tissue repair processes in equine asthma. Sci Rep 2018 Nov 6;8(1):16408.
                  doi: 10.1038/s41598-018-34636-9pubmed: 30401798google scholar: lookup
                7. Aslani MR, Keyhanmanesh R, Alipour MR. Increased Visfatin Expression Is Associated with Nuclear Factor-κB in Obese Ovalbumin-Sensitized Male Wistar Rat Tracheae. Med Princ Pract 2017;26(4):351-358.
                  doi: 10.1159/000475772pubmed: 28420006google scholar: lookup
                8. Korn A, Miller D, Dong L, Buckles EL, Wagner B, Ainsworth DM. Differential Gene Expression Profiles and Selected Cytokine Protein Analysis of Mediastinal Lymph Nodes of Horses with Chronic Recurrent Airway Obstruction (RAO) Support an Interleukin-17 Immune Response. PLoS One 2015;10(11):e0142622.
                  doi: 10.1371/journal.pone.0142622pubmed: 26561853google scholar: lookup
                9. Kim DY, Ro JY, Lee CH. 20(S)-Protopanaxatriol inhibits release of inflammatory mediators in immunoglobulin E-mediated mast cell activation. J Ginseng Res 2015 Jul;39(3):189-98.
                  doi: 10.1016/j.jgr.2014.11.001pubmed: 26199549google scholar: lookup
                10. Moran G, Folch H, Henriquez C, Ortloff A, Barria M. Reaginic antibodies from horses with recurrent airway obstruction produce mast cell stimulation. Vet Res Commun 2012 Dec;36(4):251-8.
                  doi: 10.1007/s11259-012-9534-xpubmed: 23011757google scholar: lookup
                11. Racine J, Gerber V, Feutz MM, Riley CP, Adamec J, Swinburne JE, Couetil LL. Comparison of genomic and proteomic data in recurrent airway obstruction affected horses using Ingenuity Pathway Analysis®. BMC Vet Res 2011 Aug 15;7:48.
                  doi: 10.1186/1746-6148-7-48pubmed: 21843342google scholar: lookup
                12. Moran G, Buechner-Maxwell VA, Folch H, Henriquez C, Galecio JS, Perez B, Carrasco C, Barria M. Increased apoptosis of CD4 and CD8 T lymphocytes in the airways of horses with recurrent airway obstruction. Vet Res Commun 2011 Oct;35(7):447-56.
                  doi: 10.1007/s11259-011-9482-xpubmed: 21594641google scholar: lookup
                13. Giangreco A, Lu L, Mazzatti DJ, Spencer-Dene B, Nye E, Teixeira VH, Janes SM. Myd88 deficiency influences murine tracheal epithelial metaplasia and submucosal gland abundance. J Pathol 2011 Jun;224(2):190-202.
                  doi: 10.1002/path.2876pubmed: 21557220google scholar: lookup
                14. Kim DY, Park BS, Hong GU, Lee BJ, Park JW, Kim SY, Ro JY. Anti-inflammatory effects of the R2 peptide, an inhibitor of transglutaminase 2, in a mouse model of allergic asthma, induced by ovalbumin. Br J Pharmacol 2011 Jan;162(1):210-25.
                  doi: 10.1111/j.1476-5381.2010.01033.xpubmed: 20840469google scholar: lookup
                15. Blasi F, Aliberti S, Allegra L, Piatti G, Tarsia P, Ossewaarde JM, Verweij V, Nijkamp FP, Folkerts G. Chlamydophila pneumoniae induces a sustained airway hyperresponsiveness and inflammation in mice. Respir Res 2007 Nov 19;8(1):83.
                  doi: 10.1186/1465-9921-8-83pubmed: 18021431google scholar: lookup
                16. Strickland I, Ghosh S. Use of cell permeable NBD peptides for suppression of inflammation. Ann Rheum Dis 2006 Nov;65 Suppl 3(Suppl 3):iii75-82.
                  doi: 10.1136/ard.2006.058438pubmed: 17038479google scholar: lookup
                17. Matera MG, Calzetta L, Peli A, Scagliarini A, Matera C, Cazzola M. Immune sensitization of equine bronchus: glutathione, IL-1beta expression and tissue responsiveness. Respir Res 2005 Sep 15;6(1):104.
                  doi: 10.1186/1465-9921-6-104pubmed: 16164745google scholar: lookup
                18. Poynter ME, Cloots R, van Woerkom T, Butnor KJ, Vacek P, Taatjes DJ, Irvin CG, Janssen-Heininger YM. NF-kappa B activation in airways modulates allergic inflammation but not hyperresponsiveness. J Immunol 2004 Dec 1;173(11):7003-9.
                  doi: 10.4049/jimmunol.173.11.7003pubmed: 15557197google scholar: lookup
                19. Kumar A, Takada Y, Boriek AM, Aggarwal BB. Nuclear factor-kappaB: its role in health and disease. J Mol Med (Berl) 2004 Jul;82(7):434-48.
                  doi: 10.1007/s00109-004-0555-ypubmed: 15175863google scholar: lookup
                20. Blasi F, Damato S, Cosentini R, Tarsia P, Raccanelli R, Centanni S, Allegra L. Chlamydia pneumoniae and chronic bronchitis: association with severity and bacterial clearance following treatment. Thorax 2002 Aug;57(8):672-6.
                  doi: 10.1136/thorax.57.8.672pubmed: 12149525google scholar: lookup
                21. Poynter ME, Irvin CG, Janssen-Heininger YM. Rapid activation of nuclear factor-kappaB in airway epithelium in a murine model of allergic airway inflammation. Am J Pathol 2002 Apr;160(4):1325-34.
                  doi: 10.1016/s0002-9440(10)62559-xpubmed: 11943717google scholar: lookup
                22. Turlej RK, Fiévez L, Sandersen CF, Dogné S, Kirschvink N, Lekeux P, Bureau F. Enhanced survival of lung granulocytes in an animal model of asthma: evidence for a role of GM-CSF activated STAT5 signalling pathway. Thorax 2001 Sep;56(9):696-702.
                  doi: 10.1136/thorax.56.9.696pubmed: 11514690google scholar: lookup
                23. Askarizadeh F, Karav S, Jamialahmadi T, Sahebkar A. Impact of statin therapy on CD40:CD40L signaling: mechanistic insights and therapeutic opportunities. Pharmacol Rep 2025 Feb;77(1):43-71.
                  doi: 10.1007/s43440-024-00678-2pubmed: 39680334google scholar: lookup
                Subscribe to our newsletter
                Join 99,928 horse owners like you who receive our email updates on horse health and nutrition.