Toll-like receptor 2, 3, and 4 expression and function in human airway smooth muscle - 20/08/11
Reprint requests: Kian Fan Chung, MD, National Heart and Lung Institute, Imperial College, Dovehouse St, SW3 6LY, London, United Kingdom.London, United Kingdom
Abstract |
Background |
Host defense against microbial pathogens is elicited through the innate immune system by means of Toll-like receptors (TLRs). Airway smooth muscle cells (ASMCs) display proinflammatory and immunomodulatory functions. ASMCs might participate in airway inflammatory responses associated with innate immune activation.
Objectives |
We determined the effects of cytokines, TLR ligands, and corticosteroids on TLR expression and function in human ASMCs.
Methods |
Real-time PCR and flow cytometry were used to assess TLR mRNA and protein expression, respectively. ASMCs were stimulated with TLR ligands, and chemokine release was measured by means of ELISA.
Results |
ASMCs expressed TLR1 to TLR10 mRNA, and TLR2 and TLR3 protein expression was demonstrated. TNF-⍺ and double-stranded RNA (dsRNA; TLR3 ligand) were potent inducers of TLR2 and TLR3 mRNA expression, and both stimuli had additive or synergistic effects with IFN-γ on TLR2 and TLR4, but not TLR3, mRNA expression. Peptidoglycan (TLR2 ligand) and LPS (TLR4 ligand) weakly enhanced TLR2 mRNA expression. Peptidoglycan, dsRNA, and LPS induced IL-8 and eotaxin release, with dsRNA being most potent. dsRNA also modulated cytokine-induced chemokine release in a differential manner. Dexamethasone inhibited cytokine- and ligand-induced TLR2, TLR3, and TLR4 expression and chemokine release. However, dexamethasone potentiated TLR2 expression induced by combined IFN-γ and TNF-⍺ stimulation.
Conclusion |
Expression of TLR2, TLR3, and TLR4 is regulated by cytokines and TLR ligands, and their activation mediates chemokine release in ASMCs.
Clinical implications |
Proinflammatory responses mediated by activation of pathogen-recognition receptors in ASMCs might contribute to infectious exacerbations of airway inflammatory conditions, such as asthma and chronic obstructive pulmonary disease.
Le texte complet de cet article est disponible en PDF.Key words : Toll-like receptor, human airway smooth muscle, double-stranded RNA, peptidoglycan, lipopolysaccharide, IFN-γ, TNF-⍺, eotaxin, IL-8, corticosteroid
Abbreviations used : ASMC, dsRNA, NOD, PGN, TLR
Plan
| Supported by a grant from the Wellcome Trust. Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 118 - N° 3
P. 641-648 - septembre 2006 Retour au numéro
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