CD40 and OX40 ligand are increased on stimulated asthmatic airway smooth muscle - 18/08/11
, Anita E. Blake, BSc c, Sarah Boustany, MSc b, Peter R.A. Johnson, PhD a, b, Carol L. Armour, PhD c, Judith L. Black, MBBS, PhD a, b, Nicholas H. Hunt, PhD d, J. Margaret Hughes, PhD c
Reprint requests: Janette K. Burgess, PhD, Respiratory Research Group, Department of Pharmacology, Bosch Building, D05, University of Sydney, Sydney, NSW, Australia, 2006.Sydney, Australia
Abstract |
Background |
Severe, persistent asthma is characterized by airway smooth muscle hyperplasia, inflammatory cell infiltration into the smooth muscle, and increased expression of many cytokines, including IL-4, IL-13, IL-1β, and TNF-⍺. These cytokines have the potential to alter the expression of surface receptors such as CD40 and OX40 ligand on the airway smooth muscle cell.
Objective |
To examine whether cytokines alter expression of CD40 and OX40 ligand on airway smooth muscle cells and identify any differences in response between asthmatic and nonasthmatic airway smooth muscle cells.
Methods |
We used flow cytometry and immunohistochemistry to detect CD40 and OX40 ligand on airway smooth muscle cells cultured in the presence of TNF-⍺, IL-1β, IL-4, or IL-13. Prostaglandin E2 levels were assessed by ELISA.
Results |
TNF-⍺ increased expression of both CD40 and OX40 ligand on both asthmatic and nonasthmatic airway smooth muscle cells. The level of expression was significantly greater on the asthmatic cells. IL-1β alone had no effect, but it attenuated the TNF-induced expression of both CD40 and OX40 ligand. The mechanism of inhibition was COX-dependent for CD40 and was COX-independent but cyclic AMP–dependent for OX40 ligand. IL-4 and IL-13 had no effect.
Conclusion |
Our study has demonstrated that TNF-⍺ and IL-1β have the potential to modulate differentially the interactions between cells present in the inflamed airways of a patient with asthma and therefore to contribute to the regulation of airway inflammation and remodeling.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, inflammation, CD40, OX40 ligand, TNF, IL-1β, prostaglandin E2, human airway smooth muscle cells
Abbreviations used : ASM, cAMP, DMEM, FITC, ICAM, MFI, NF-κB, OX40L, PGE2, 8-Bromo–cAMP
Plan
| Supported by the National Health and Medical Research Council. Dr Burgess is supported by National Health and Medical Research Council Peter Doherty Fellowship #165722. |
Vol 115 - N° 2
P. 302-308 - février 2005 Retour au numéro
Article précédent
- Toll-like receptor 2 ligands activate human basophils for both IgE-dependent and IgE-independent secretion
- Anja P. Bieneman, Kristin L. Chichester, Yi-Hsing Chen, John T. Schroeder
- TH1-mediated airway hyperresponsiveness independent of neutrophilic inflammation
- Junqing Cui, Stephen Pazdziorko, Joy S. Miyashiro, Paresh Thakker, Jeffrey W. Pelker, Charlene DeClercq, Aiping Jiao, Jason Gunn, Lawrence Mason, John P. Leonard, Cara M.M. Williams, Suzana Marusic
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?