help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 WILSON, S. J.
Right arrow Articles by HOLGATE, S. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by WILSON, S. J.
Right arrow Articles by HOLGATE, S. T.

Am. J. Respir. Crit. Care Med., Volume 164, Number 6, September 2001, 1047-1052

Effects of Budesonide and Formoterol on NF-kappa B, Adhesion Molecules, and Cytokines in Asthma

SUSAN J. WILSON, ANNIKA WALLIN, GIOVANNI DELLA-CIOPPA, THOMAS SANDSTRÖM, and STEPHEN T. HOLGATE

Respiratory Cell and Molecular Biology Research Division, School of Medicine, University of Southampton, Southhampton, United Kingdom; University Hospital of Northern Sweden, Umeå, Sweden; and Novartis, Horsham Research Centre, Horsham, United Kingdom

The asthmatic inflammatory response can be attenuated by corticosteroids and in part by beta 2-agonists. We investigated if these effects are accompanied by a downregulation in nuclear factor kappa B (NF-kappa B), a transcription factor regulating many of the cytokine and adhesion molecule genes expressed in allergic inflammation. Bronchial biopsies were taken before and after 8 wk treatment with formoterol, budesonide, or placebo from atopic asthmatics. Biopsies were processed into glycol methacrylate and stained immunohistochemically for eosinophils (as an index of inflammation), activated and total NF-kappa B, adhesion molecules, and cytokines. After budesonide treatment there was a significant decrease in the number of submucosal cells staining for total NF-kappa B, granulocyte macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha ), accompanied by a significant decrease in mucosal eosinophils and expression of vascular cell adhesion molecule-1 (VCAM-1) in the endothelium and interleukin-8 (IL-8) in the epithelium. After formoterol treatment there was a significant decrease in eosinophils and the epithelial expression of activated NF-kappa B, but these changes were not accompanied by reduced immunoreactivity for adhesion molecules or cytokines. We conclude that at least some of the therapeutic efficacy of inhaled corticosteroids is mediated through inhibition of NF-kappa B-regulated gene expression, whereas the reduction in airway eosinophilia by long-acting beta 2-agonists probably operates through alternative pathways.

Keywords: budesonide; formoterol; NF-kappa B; immunohistochemistry; asthma




This article has been cited by other articles:


Home page
 Eur Respir JHome page
J. Loven, N. Svitacheva, A. Jerre, A. Miller-Larsson, and S. H. Korn
Anti-inflammatory activity of {beta}2-agonists in primary lung epithelial cells is independent of glucocorticoid receptor
Eur. Respir. J., November 1, 2007; 30(5): 848 - 856.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
M. R. Edwards, M. W. Johnson, and S. L. Johnston
Combination Therapy: Synergistic Suppression of Virus-Induced Chemokines in Airway Epithelial Cells
Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 616 - 624.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
S. Baouz, J. Giron-Michel, B. Azzarone, M. Giuliani, F. Cagnoni, S. Olsson, R. Testi, G. Gabbiani, and G. W. Canonica
Lung myofibroblasts as targets of salmeterol and fluticasone propionate: inhibition of {alpha}-SMA and NF-{kappa}B
Int. Immunol., November 1, 2005; 17(11): 1473 - 1481.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. A. Birrell, E. Hardaker, S. Wong, K. McCluskie, M. Catley, J. De Alba, R. Newton, S. Haj-Yahia, K. T. Pun, C. J. Watts, et al.
I{kappa}-B Kinase-2 Inhibitor Blocks Inflammation in Human Airway Smooth Muscle and a Rat Model of Asthma
Am. J. Respir. Crit. Care Med., October 15, 2005; 172(8): 962 - 971.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
K. Maneechotesuwan, S. Essilfie-Quaye, S. Meah, C. Kelly, S. A. Kharitonov, I. M. Adcock, and P. J. Barnes
Formoterol Attenuates Neutrophilic Airway Inflammation in Asthma
Chest, October 1, 2005; 128(4): 1936 - 1942.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
W. J. Howat, A. Warford, J. N. Mitchell, K. F. Clarke, J. S. Conquer, and J. McCafferty
Resin Tissue Microarrays: a Universal Format for Immunohistochemistry
J. Histochem. Cytochem., October 1, 2005; 53(10): 1189 - 1197.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
H. Yoshisue, S. M. Puddicombe, S. J. Wilson, H. M. Haitchi, R. M. Powell, D. I. Wilson, A. Pandit, A. E. Berger, D. E. Davies, S. T. Holgate, et al.
Characterization of Ciliated Bronchial Epithelium 1, a Ciliated Cell-Associated Gene Induced During Mucociliary Differentiation
Am. J. Respir. Cell Mol. Biol., November 1, 2004; 31(5): 491 - 500.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
M. Roth, P. R.A. Johnson, P. Borger, M. P. Bihl, J. J. Rudiger, G. G. King, Q. Ge, K. Hostettler, J. K. Burgess, J. L. Black, et al.
Dysfunctional Interaction of C/EBP{alpha} and the Glucocorticoid Receptor in Asthmatic Bronchial Smooth-Muscle Cells
N. Engl. J. Med., August 5, 2004; 351(6): 560 - 574.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. Castro, S. R. Bloch, M. V. Jenkerson, S. DeMartino, D. L. Hamilos, R. B. Cochran, X. E. L. Zhang, H. Wang, J. P. Bradley, K. B. Schechtman, et al.
Asthma Exacerbations after Glucocorticoid Withdrawal Reflects T Cell Recruitment to the Airway
Am. J. Respir. Crit. Care Med., April 1, 2004; 169(7): 842 - 849.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
R. Gagliardo, P. Chanez, M. Mathieu, A. Bruno, G. Costanzo, C. Gougat, I. Vachier, J. Bousquet, G. Bonsignore, and A. M. Vignola
Persistent Activation of Nuclear Factor-{kappa}B Signaling Pathway in Severe Uncontrolled Asthma
Am. J. Respir. Crit. Care Med., November 15, 2003; 168(10): 1190 - 1198.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
S. Tanaka, H. Tanaka, and S. Abe
High Dose of Inhaled Fluticasone Reduces High Levels of Urinary Leukotriene E4 in the Early Morning in Mild and Moderate Nocturnal Asthma
Chest, November 1, 2003; 124(5): 1768 - 1773.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. E. Poynter, C. G. Irvin, and Y. M. W. Janssen-Heininger
A Prominent Role for Airway Epithelial NF-{kappa}B Activation in Lipopolysaccharide-Induced Airway Inflammation
J. Immunol., June 15, 2003; 170(12): 6257 - 6265.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
I. Jibiki, S. Hashimoto, S. Maruoka, Y. Gon, A. Matsuzawa, H. Nishitoh, H. Ichijo, and T. Horie
Apoptosis Signal-Regulating Kinase 1-Mediated Signaling Pathway Regulates Nitric Oxide-Induced Activator Protein-1 Activation in Human Bronchial Epithelial Cells
Am. J. Respir. Crit. Care Med., March 15, 2003; 167(6): 856 - 861.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
P A Beckett and P H Howarth
Pharmacotherapy and airway remodelling in asthma?
Thorax, February 1, 2003; 58(2): 163 - 174.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
E. Ohga, T. Tomita, H. Wada, H. Yamamoto, T. Nagase, and Y. Ouchi
Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1
J Appl Physiol, January 1, 2003; 94(1): 179 - 184.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. Faisy, E. Naline, J.-L. Diehl, X. Emonds-Alt, T. Chinet, and C. Advenier
In vitro sensitization of human bronchus by beta 2-adrenergic agonists
Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L1033 - L1042.
[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 2001
Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 598 - 618.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2001 American Thoracic Society