Toll-like receptor 2, 3, and 4 expression and function in human airway smooth muscle
| Autor: | Rex Stanbridge, Kian Fan Chung, Shaoping Xie, Razao Issa, Nadia Khorasani, Maria B. Sukkar, Onn Min Kon |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Eotaxin
Chemokine Myocytes Smooth Muscle Immunology Bronchi Cell Separation Ligands Proinflammatory cytokine Humans Immunology and Allergy RNA Messenger Interleukin 8 Lung Cells Cultured Toll-like receptor biology Toll-Like Receptors Toll-Like Receptor 2 Toll-Like Receptor 3 Toll-Like Receptor 4 TLR2 TLR3 TLR4 biology.protein Chemokines |
| Zdroj: | Journal of Allergy and Clinical Immunology. 118:641-648 |
| ISSN: | 0091-6749 |
| Popis: | 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-α 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-α 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. |
| Databáze: | OpenAIRE |
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