help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on July 31, 2003, doi:10.1164/rccm.200205-479OC

Am. J. Respir. Crit. Care Med., Volume 168, Number 10, November 2003, 1190-1198

A more recent version of this article appeared on November 15, 2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200205-479OCv1
168/10/1190    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gagliardo, R.
Right arrow Articles by Vignola, A. M
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gagliardo, R.
Right arrow Articles by Vignola, A. M

Submitted on May 28, 2002
Accepted on July 30, 2003

Persistent activation of NF-{kappa}B signalling pathway in severe uncontrolled asthma

Rosalia Gagliardo1*, Pascal Chanez2, Marc Mathieu2, Andreina Bruno1, Giorgia Costanzo1, Claire Gougat2, Isabelle Vachier2, Jean Bousquet2, Giovanni Bonsignore3, and Antonio M Vignola4

1 Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy, 2 U454 and Service des Maladies Respiratoires, Institut National de la Sante et de la Recherche Medicale, Montpellier, France, 3 Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy; Istituto di Medicina Generale e Pneumologia, Universita' degli Studi di Palermo, Palermo, Italy, 4 Istituto di Medicina Generale e Pneumologia, Universita' degli Studi di Palermo, Palermo, Italy; Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy

* To whom correspondence should be addressed. E-mail: gagliardo.r{at}iol.it.

The transcription factor NF-kB is inactive when bound to its inhibitory protein IkBa. Upon cell stimulation with inflammatory signals, IkBa is phosphorylated by IkB kinases (IKK) and subsequently degraded. Freed NF-kB then induces expression of cytokines like GM-CSF, IL-8 and RANTES. These mediators are overexpressed in asthma and are down-regulated by glucocorticoids (GCs) through NF-kB activity repression. However, high levels of GM-CSF, IL-8 and RANTES are released by PBMC isolated from severe asthmatics despite continuous systemic GC treatment. We report that these mediators are markedly decreased by pyrrolidinedithiocarbamate, an inhibitor of NF-kB activation. To further characterize the persistent NF-kB activation in severe asthma, we analyzed expression of various components of this activation pathway in healthy subjects and in asthmatics with mild controlled, moderate and severe uncontrolled disease. We found high amount of phosphorylated-IkBa characterizing the three asthmatic groups. Western blot analyses indicated that in PBMC the IKKb and p65 levels were greater in moderate and severe asthmatics than in normals. EMSA and immunocytochemistry showed a greater activation status of p65 in severe asthmatics. Our data suggest that exaggerated NF-kB activation perpetuates inflammatory mediators production in severe asthma.
Key words: severe asthma, inflammation, glucocorticoids, nuclear factor-kappaB.




This article has been cited by other articles:


Home page
 Am. J. Respir. Crit. Care Med.Home page
J. H. Kang, B. S. Kim, T. G. Uhm, S.-H. Lee, G. R. Lee, C.-S. Park, and I. Y. Chung
{gamma}-Secretase Inhibitor Reduces Allergic Pulmonary Inflammation by Modulating Th1 and Th2 Responses
Am. J. Respir. Crit. Care Med., May 15, 2009; 179(10): 875 - 882.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
Z. Bao, S. Guan, C. Cheng, S. Wu, S. H. Wong, D. M. Kemeny, B. P. Leung, and W. S. F. Wong
A Novel Antiinflammatory Role for Andrographolide in Asthma via Inhibition of the Nuclear Factor-{kappa}B Pathway
Am. J. Respir. Crit. Care Med., April 15, 2009; 179(8): 657 - 665.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. P. Chapoval, A. Al-Garawi, J. M. Lora, I. Strickland, B. Ma, P. J. Lee, R. J. Homer, S. Ghosh, A. J. Coyle, and J. A. Elias
Inhibition of NF-{kappa}B Activation Reduces the Tissue Effects of Transgenic IL-13
J. Immunol., November 15, 2007; 179(10): 7030 - 7041.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
Z. Bao, S. Lim, W. Liao, Y. Lin, C. Thiemermann, B. P. Leung, and W. S. F. Wong
Glycogen Synthase Kinase-3beta Inhibition Attenuates Asthma in Mice
Am. J. Respir. Crit. Care Med., September 1, 2007; 176(5): 431 - 438.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
C. Thompson, A. Cloutier, Y. Bosse, M. Thivierge, C. L. Gouill, P. Larivee, P. P. McDonald, J. Stankova, and M. Rola-Pleszczynski
CysLT1 Receptor Engagement Induces Activator Protein-1- and NF-{kappa}B-Dependent IL-8 Expression
Am. J. Respir. Cell Mol. Biol., December 1, 2006; 35(6): 697 - 704.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
W. M. Abraham, A. Ahmed, I. Serebriakov, I. T. Lauredo, J. Bassuk, J. A. Adams, and M. A. Sackner
Whole-Body Periodic Acceleration Modifies Experimental Asthma in Sheep
Am. J. Respir. Crit. Care Med., October 1, 2006; 174(7): 743 - 752.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
M. A. Birrell, S. Wong, E. L. Hardaker, M. C. Catley, K. McCluskie, M. Collins, S. Haj-Yahia, and M. G. Belvisi
I{kappa}B Kinase-2-Independent and -Dependent Inflammation in Airway Disease Models: Relevance of IKK-2 Inhibition to the Clinic
Mol. Pharmacol., June 1, 2006; 69(6): 1791 - 1800.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. H. Broide, T. Lawrence, T. Doherty, J. Y. Cho, M. Miller, K. McElwain, S. McElwain, and M. Karin
Allergen-induced peribronchial fibrosis and mucus production mediated by I{kappa}B kinase {beta}-dependent genes in airway epithelium
PNAS, December 6, 2005; 102(49): 17723 - 17728.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
B. D. Levy, C. Bonnans, E. S. Silverman, L. J. Palmer, G. Marigowda, E. Israel, and for the Severe Asthma Research Program, National H
Diminished Lipoxin Biosynthesis in Severe Asthma
Am. J. Respir. Crit. Care Med., October 1, 2005; 172(7): 824 - 830.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. Wenzel
Severe Asthma in Adults
Am. J. Respir. Crit. Care Med., July 15, 2005; 172(2): 149 - 160.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. J. Tobin
Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2003
Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 265 - 276.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2003 American Thoracic Society 		  CCM abstracts