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Journal of immunology (Baltimore, Md. : 1950)2000; 165(10); 5822-5830; doi: 10.4049/jimmunol.165.10.5822

Mechanisms of persistent NF-kappa B activity in the bronchi of an animal model of asthma.

Abstract: In most cells trans-activating NF-kappaB induces many inflammatory proteins as well as its own inhibitor, IkappaB-alpha, thus assuring a transient response upon stimulation. However, NF-kappaB-dependent inflammatory gene expression is persistent in asthmatic bronchi, even after allergen eviction. In the present report we used bronchial brushing samples (BBSs) from heaves-affected horses (a spontaneous model of asthma) to elucidate the mechanisms by which NF-kappaB activity is maintained in asthmatic airways. NF-kappaB activity was high in granulocytic and nongranulocytic BBS cells. However, NF-kappaB activity highly correlated to granulocyte percentage and was only abrogated after granulocytic death in cultured BBSs. Before granulocytic death, NF-kappaB activity was suppressed by simultaneous addition of neutralizing anti-IL-1beta and anti-TNF-alpha Abs to the medium of cultured BBSs. Surprisingly, IkappaB-beta, whose expression is not regulated by NF-kappaB, unlike IkappaB-alpha, was the most prominent NF-kappaB inhibitor found in BBSs. The amounts of IkappaB-beta were low in BBSs obtained from diseased horses, but drastically increased after addition of the neutralizing anti-IL-1beta and anti-TNF-alpha Abs. These results indicate that sustained NF-kappaB activation in asthmatic bronchi is driven by granulocytes and is mediated by IL-1beta and TNF-alpha. Moreover, an imbalance between high levels of IL-1beta- and TNF-alpha-mediated IkappaB-beta degradation and low levels of IkappaB-beta synthesis is likely to be the mechanism preventing NF-kappaB deactivation in asthmatic airways before granulocytic death.
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Publication Date: 2000-11-09 PubMed ID: 11067942DOI: 10.4049/jimmunol.165.10.5822Google Scholar: Lookup
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  • 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 article focuses on studying the sustained activation of NF-kappaB, a crucial protein involved in inflammatory responses, in the airways of horses with spontaneous asthma. The authors find that this prolonged activation, contrary to usual cellular responses, is influenced by granulocytes (a type of immune cells) and specific inflammatory signals, IL-1beta and TNF-alpha, which also regulate a key NF-kappaB inhibitor, IkappaB-beta.

Research Context and Aim

  • The article centers around NF-kappaB, a protein that induces many inflammatory responses within cells, including the production of its inhibitor, IkappaB-alpha. Usually, this initiates a transient response. However, in the context of asthma, the inflammatory gene expression facilitated by NF-kappaB remains persistent, even without allergen presence.
  • The aim of the paper is to understand the mechanisms that sustain NF-kappaB activity in the bronchi (airways) of asthmatic animals. The authors utilize bronchial brushing samples (BBSs) from asthma-affected horses as their model system.

Research Findings and Methodology

  • Through their investigation, they find high NF-kappaB activity in both granulocytic (involving granulocytes, a type of immune cells) and non-granulocytic BBS cells.
  • The activity of NF-kappaB was found to be strongly correlated to the percentage of granulocytes. NF-kappaB activity ceased only after these granulocytes have died.
  • The authors managed to suppress NF-kappaB activity before granulocyte death by adding neutralizing antibodies to IL-1beta and TNF-alpha (inflammatory mediators) together to the culture medium.
  • IkappaB-beta was the major NF-kappaB inhibitor found in these BBSs, unlike IkappaB-alpha which usually regulates NF-kappaB. Interestingly, IkappaB-beta’s expression was not regulated by NF-kappaB.
  • The authors saw low levels of IkappaB-beta in the BBSs from diseased horses, which substantially increased after the addition of neutralizing antibodies against IL-1beta and TNF-alpha.

Conclusion and Implications

  • Overall, the results suggest that the sustained activation of NF-kappaB in the airways of asthmatic horses is driven primarily by granulocytes and mediated by the inflammatory regulators IL-1beta and TNF-alpha.
  • Furthermore, an imbalance between excessive IL-1beta- and TNF-alpha-mediated IkappaB-beta degradation and its low-level synthesis might be preventing NF-kappaB deactivation before the death of granulocytes in asthmatic airways.
  • These findings provide key insights into the mechanistic aspects of chronic inflammation in asthma and can guide future research for potential therapeutic interventions for asthma.

Cite This Article

APA
Bureau F, Delhalle S, Bonizzi G, Fiévez L, Dogné S, Kirschvink N, Vanderplasschen A, Merville MP, Bours V, Lekeux P. (2000). Mechanisms of persistent NF-kappa B activity in the bronchi of an animal model of asthma. J Immunol, 165(10), 5822-5830. https://doi.org/10.4049/jimmunol.165.10.5822

Publication

Journal of immunology (Baltimore, Md. : 1950)
ISSN: 0022-1767
NlmUniqueID: 2985117R
Country: United States
Language: English
Volume: 165
Issue: 10
Pages: 5822-5830

Researcher Affiliations

Bureau, F
  • Departments of Physiology and Immunology/Vaccinology, Faculty of Veterinary Medicine, and Laboratory of Medical Chemistry/Medical Oncology, Faculty of Medicine, University of Liege, Liege, Belgium.
Delhalle, S
    Bonizzi, G
      Fiévez, L
        Dogné, S
          Kirschvink, N
            Vanderplasschen, A
              Merville, M P
                Bours, V
                  Lekeux, P

                    MeSH Terms

                    • Airway Obstruction / immunology
                    • Airway Obstruction / metabolism
                    • Airway Obstruction / pathology
                    • Airway Obstruction / veterinary
                    • Animals
                    • Asthma / immunology
                    • Asthma / metabolism
                    • Asthma / pathology
                    • Asthma / veterinary
                    • Bronchi / immunology
                    • Bronchi / metabolism
                    • Bronchi / pathology
                    • Bronchoalveolar Lavage Fluid / cytology
                    • Cell Death
                    • Cell Survival
                    • Cells, Cultured
                    • DNA-Binding Proteins / antagonists & inhibitors
                    • DNA-Binding Proteins / metabolism
                    • DNA-Binding Proteins / pharmacology
                    • Dimerization
                    • Disease Models, Animal
                    • Granulocytes / metabolism
                    • Granulocytes / pathology
                    • Horse Diseases / immunology
                    • Horse Diseases / metabolism
                    • Horse Diseases / pathology
                    • Horses
                    • I-kappa B Proteins
                    • Immune Sera / pharmacology
                    • Interleukin-1 / immunology
                    • Leukocyte Count
                    • NF-kappa B / antagonists & inhibitors
                    • NF-kappa B / metabolism
                    • Transcription Factor RelA
                    • Tumor Necrosis Factor-alpha / immunology

                    Citations

                    This article has been cited 25 times.
                    1. Babu V, Kapkoti DS, Binwal M, Bhakuni RS, Shanker K, Singh M, Tandon S, Mugale MN, Kumar N, Bawankule DU. Liquiritigenin, isoliquiritigenin rich extract of glycyrrhiza glabra roots attenuates inflammation in macrophages and collagen-induced arthritis in rats. Inflammopharmacology 2023 Apr;31(2):983-996.
                      doi: 10.1007/s10787-023-01152-wpubmed: 36947299google scholar: lookup
                    2. 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
                    3. Simões J, Batista M, Tilley P. The Immune Mechanisms of Severe Equine Asthma-Current Understanding and What Is Missing. Animals (Basel) 2022 Mar 16;12(6).
                      doi: 10.3390/ani12060744pubmed: 35327141google 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. Wei DZ, Guo XY, Lin LN, Lin MX, Gong YQ, Ying BY, Huang MY. Effects of Angelicin on Ovalbumin (OVA)-Induced Airway Inflammation in a Mouse Model of Asthma. Inflammation 2016 Dec;39(6):1876-1882.
                      doi: 10.1007/s10753-016-0423-2pubmed: 27581277google scholar: lookup
                    6. Riva L, Thiry M, Lebrun M, L'homme L, Piette J, Sadzot-Delvaux C. Deletion of the ORF9p acidic cluster impairs the nuclear egress of varicella-zoster virus capsids. J Virol 2015 Feb;89(4):2436-41.
                      doi: 10.1128/JVI.03215-14pubmed: 25473054google scholar: lookup
                    7. 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
                    8. Lin LJ, Lin CC, Wang SD, Chao YP, Kao ST. The Immunomodulatory Effect of You-Gui-Wan on Dermatogoides-pteronyssinus-Induced Asthma. Evid Based Complement Alternat Med 2012;2012:476060.
                      doi: 10.1155/2012/476060pubmed: 22675381google scholar: lookup
                    9. Toussaint M, Fievez L, Desmet CJ, Pirottin D, Farnir F, Bureau F, Lekeux P. Increased hypoxia-inducible factor 1α expression in lung cells of horses with recurrent airway obstruction. BMC Vet Res 2012 May 23;8:64.
                      doi: 10.1186/1746-6148-8-64pubmed: 22621400google scholar: lookup
                    10. Riechelmann H. Cellular and molecular mechanisms in environmental and occupational inhalation toxicology. GMS Curr Top Otorhinolaryngol Head Neck Surg 2004;3:Doc02.
                      pubmed: 22073044
                    11. 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
                    12. Lee JH, Wang LC, Yu HH, Lin YT, Yang YH, Chiang BL. Type I IL-1 receptor (IL-1RI) as potential new therapeutic target for bronchial asthma. Mediators Inflamm 2010;2010:567351.
                      doi: 10.1155/2010/567351pubmed: 20671916google scholar: lookup
                    13. Sheller JR, Polosukhin VV, Mitchell D, Cheng DS, Peebles RS, Blackwell TS. Nuclear factor kappa B induction in airway epithelium increases lung inflammation in allergen-challenged mice. Exp Lung Res 2009 Dec;35(10):883-95.
                      doi: 10.3109/01902140903019710pubmed: 19995280google scholar: lookup
                    14. Clarke D, Damera G, Sukkar MB, Tliba O. Transcriptional regulation of cytokine function in airway smooth muscle cells. Pulm Pharmacol Ther 2009 Oct;22(5):436-45.
                      doi: 10.1016/j.pupt.2009.04.003pubmed: 19393330google scholar: lookup
                    15. Zhou LF, Zhu Y, Cui XF, Xie WP, Hu AH, Yin KS. Arsenic trioxide, a potent inhibitor of NF-kappaB, abrogates allergen-induced airway hyperresponsiveness and inflammation. Respir Res 2006 Dec 20;7(1):146.
                      doi: 10.1186/1465-9921-7-146pubmed: 17178007google 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. Moynagh PN. The interleukin-1 signalling pathway in astrocytes: a key contributor to inflammation in the brain. J Anat 2005 Sep;207(3):265-9.
                      doi: 10.1111/j.1469-7580.2005.00445.xpubmed: 16185251google scholar: lookup
                    18. 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
                    19. Bai Y, Onuma H, Bai X, Medvedev AV, Misukonis M, Weinberg JB, Cao W, Robidoux J, Floering LM, Daniel KW, Collins S. Persistent nuclear factor-kappa B activation in Ucp2-/- mice leads to enhanced nitric oxide and inflammatory cytokine production. J Biol Chem 2005 May 13;280(19):19062-9.
                      doi: 10.1074/jbc.M500566200pubmed: 15757894google scholar: lookup
                    20. 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
                    21. Schroeter CH, Schaub B, Gold DR, Contreras PJ, Manrique O, Gillman MW, Weiss S, Palmer LJ, Perkins D, Finn PW. Nuclear factor kappa B activation in human cord blood mononuclear cells. Pediatr Res 2004 Aug;56(2):212-8.
                      doi: 10.1203/01.PDR.0000132850.33375.D0pubmed: 15181194google scholar: lookup
                    22. 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
                    23. 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
                    24. Vancurova I, Wu R, Miskolci V, Sun S. Increased p50/p50 NF-kappaB activation in human papillomavirus type 6- or type 11-induced laryngeal papilloma tissue. J Virol 2002 Feb;76(3):1533-6.
                      doi: 10.1128/jvi.76.3.1533-1536.2002pubmed: 11773428google scholar: lookup
                    25. Abdelmawgood IA, Mahana NA, Badr AM, Mohamed AS. Echinochrome exhibits anti-asthmatic activity through the suppression of airway inflammation, oxidative stress, and histopathological alterations in ovalbumin-induced asthma in BALB/c mice. Naunyn Schmiedebergs Arch Pharmacol 2024 Mar;397(3):1803-1815.
                      doi: 10.1007/s00210-023-02678-0pubmed: 37750936google scholar: lookup
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