Ligation of Toll-Like Receptor 3 Differentially Regulates M2 and M3 Muscarinic Receptor Expression and Function in Human Airway Smooth Muscle Cells
| العنوان: | Ligation of Toll-Like Receptor 3 Differentially Regulates M2 and M3 Muscarinic Receptor Expression and Function in Human Airway Smooth Muscle Cells |
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| المؤلفون: | Yukiyoshi Yanagihara, Hirotaka Morishima, Keiichi Kajiwara, Kazuo Akiyama |
| المصدر: | International Archives of Allergy and Immunology. 145:163-174 |
| بيانات النشر: | S. Karger AG, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | viruses, Myocytes, Smooth Muscle, Immunology, Muscarinic Antagonists, Biology, Leukotriene D4, eIF-2 Kinase, Histamine receptor, Calcium flux, Cyclic AMP, Humans, Immunology and Allergy, Calcium Signaling, Receptors, Histamine H1, 2-Aminopurine, Receptor, Cells, Cultured, Receptor, Muscarinic M3, Receptors, Leukotriene, Receptor, Muscarinic M2, Toll-like receptor, Colforsin, Membrane Proteins, Muscarinic acetylcholine receptor M3, Chloroquine, General Medicine, respiratory system, Protein kinase R, Toll-Like Receptor 3, Poly I-C, Gene Expression Regulation, Interleukin-21 receptor, TLR3, Bronchial Hyperreactivity, Histamine, Signal Transduction |
| الوصف: | Background: Viral infection causes asthma exacerbations and airway hyperreactivity. Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA) of viral or synthetic origin in a fashion different from protein kinase R (PKR). The aim of this study was to examine the expression and function of TLR3 in human airway smooth muscle (ASM) cells. Methods: Expression of TLR3 and muscarinic receptor (MR), histamine receptor (HR), and cysteinyl leukotriene receptor (CysLTR) subtypes was analyzed by quantitative real-time PCR, flow cytometry, or Western blotting. It was assessed whether ASM cells respond to polyinosinic-polycytidylic acid (poly I:C), a synthetic analog of dsRNA, with alterations in M2R, M3R, H1R, and CysLT1R expression. The function of these subtypes was evaluated by cholinergic regulation of forskolin-stimulated cyclic AMP accumulation or by mobilization of intracellular calcium upon stimulation. Results: ASM cells expressed TLR3 and PKR, and intracellular TLR3 expression was demonstrated. Poly I:C caused decreased M2R and increased M3R expression, without affecting H1R and CysLT1R expression. Poly I:C-treated cells showed decreased cholinergic inhibition of forskolin-stimulated cyclic AMP accumulation and enhanced calcium flux in response to acetylcholine, but not to histamine and LTD4. These modulating effects of poly I:C were reversed by chloroquine, but not by 2-aminopurine. Conclusions: The data indicate that poly I:C internalized by ASM cells differentially regulates M2R and M3R expression and function by interacting with TLR3 rather than with PKR, suggesting that these changes may contribute to airway hyperreactivity. |
| تدمد: | 1423-0097 1018-2438 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5ef6d8473488da9922c184dc5546c5f0Test https://doi.org/10.1159/000108141Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....5ef6d8473488da9922c184dc5546c5f0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14230097 10182438 |
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