Cytokines enhance airway smooth muscle contractility in response to acetylcholine and neurokinin A
| العنوان: | Cytokines enhance airway smooth muscle contractility in response to acetylcholine and neurokinin A |
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| المؤلفون: | Raffaele Scicchitano, Mark Holmes, Ann M. Reynolds |
| المصدر: | Respirology. 5:153-160 |
| بيانات النشر: | Wiley, 2000. |
| سنة النشر: | 2000 |
| مصطلحات موضوعية: | Pulmonary and Respiratory Medicine, medicine.medical_specialty, Neurokinin A, medicine.medical_treatment, chemistry.chemical_element, Calcium, Calcium in biology, Bronchoconstrictor Agents, Contractility, chemistry.chemical_compound, Internal medicine, medicine, Extracellular, Animals, Sheep, Tumor Necrosis Factor-alpha, business.industry, Phosphoramidon, Muscle, Smooth, respiratory system, Acetylcholine, Bronchodilator Agents, Trachea, Cytokine, Endocrinology, chemistry, Female, business, Interleukin-1, Muscle Contraction, medicine.drug |
| الوصف: | OBJECTIVE In vivo airway hyperresponsiveness has been demonstrated following inhalation of specific cytokines in normal individuals. Whether this airway hyperresponsiveness results from a direct effect of cytokines on airway smooth muscle contractility, or via changes in airway wall structure is not known. The aim of the present study was to determine the effect of the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) on airway smooth muscle contractility in vitro. METHODOLOGY Ovine tracheal smooth muscle strips were incubated for 18 h at room temperature in Dulbecco's modified Eagle's medium, supplemented with antibiotics, with IL-1beta (10 ng/mL) and TNF-alpha (100 ng/mL), in an atmosphere of 5%CO2:95%O2. Following incubation cumulative concentration-response curves to acetylcholine (ACh) and neurokinin A (NKA) were obtained. Antagonist affinity studies were performed to determine whether the cytokine-induced enhanced contractility to ACh and NKA resulted from a functional alteration to specific M3 and NK2 receptors. Cumulative concentration-response curves to NKA were performed in the presence of phosphoramidon to determine if the enhanced contractility to NKA following cytokine exposure was due to a reduction in endogenous neutral endopeptidase activity. To assess the calcium dependence of the hyperresponsiveness, cumulative concentration-responses to ACh were conducted in calcium-free Krebs'-Henseleit solution. RESULTS Pre-incubation with TNF-alpha and IL-1beta caused a significant leftward shift, and an increase in the magnitude, of the concentration-response curves to both ACh and NKA. No difference in M3 and NK2 receptor antagonist affinity (pA2) values between the control and cytokine-treated tissue was observed. Neurokinin A contractility in the presence of phosphoramidon indicated that the enhanced contractility following cytokine exposure was not due to a reduction in endogenous neutral endopeptidase activity. Removal of extracellular calcium ions attenuated the contractile response to low concentrations of ACh in the control and cytokine-pretreated tissue. However, enhanced contractility following TNF-alpha and IL-1beta pretreatment was still present. CONCLUSION Pro-inflammatory cytokines induce in vitro hyperresponsiveness in normal airway smooth muscle via a mechanism involving intracellular calcium mobilization. |
| تدمد: | 1440-1843 1323-7799 |
| DOI: | 10.1046/j.1440-1843.2000.00240.x |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b345ce35d3480220fe50cdbdd1847f5 https://doi.org/10.1046/j.1440-1843.2000.00240.x |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....1b345ce35d3480220fe50cdbdd1847f5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14401843 13237799 |
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| DOI: | 10.1046/j.1440-1843.2000.00240.x |