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首页> 外文期刊>Pulmonary pharmacology & therapeutics >dsRNA-induced expression of thymic stromal lymphopoietin (TSLP) in asthmatic epithelial cells is inhibited by a small airway relaxant.
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dsRNA-induced expression of thymic stromal lymphopoietin (TSLP) in asthmatic epithelial cells is inhibited by a small airway relaxant.

机译：小气道松弛剂可抑制dsRNA诱导的哮喘上皮细胞中胸腺基质淋巴细胞生成素（TSLP）的表达。

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RATIONALE: Thymic Stromal Lymphopoietin (TSLP) is considered a hub cytokine that activates dendritic cells and T-cells producing asthma-like Th-inflammation. Viral stimuli, a major cause of asthma exacerbations, have been shown to induce overexpression of TSLP in asthmatic epithelium. Capsazepine has multiple effects and is of interest because it relaxes human small airways. Here we have explored effects of capsazepine on viral surrogate (dsRNA)-induced TSLP and other cytokines (TNF-alpha, IL-8) in human bronchial epithelial cells (HBEC) from healthy and asthmatic donors. METHODS: HBEC obtained from healthy and asthmatic subjects were grown and stimulated with dsRNA. Cells pre-treated with capsazepine (3-30 muM), dexamethasone (0.1-10 muM) or an IkappaB-kinase inhibitor (PS1145, 30 muM) were also exposed to dsRNA (10 mug/ml). Cells and supernatants were harvested for analyses of gene expression (RT-qPCR) and protein production (ELISA,Western blot). RESULTS: dsRNA-induced TSLP, TNF-alpha, and IL-8 in asthmatic and non-asthmatic HBEC. Dexamethasone attenuated gene expression and protein release whereas capsazepine dose-dependently, and similar to a non-relaxant NFkB inhibitor (PS1145), completely inhibited dsRNA-induced TSLP and TNF-alpha in both healthy and asthmatic HBEC. Capsazepine reduced dsRNA-induced IL-8 and it prevented dsRNA-induced loss of the NF-kappaB repressor protein IkBalpha. CONCLUSION: Additional to its human small airway relaxant effects we now demonstrate that capsazepine has potent anti-inflammatory effects on viral stimulus-induced cytokines in HBEC from healthy as well as asthmatic donors. Based on these data we suggest that exploration of structure-activity amongst the multifaceted capsazepinoids is warranted in search for compounds of therapeutic value in viral-induced, steroid-resistant asthma.
机译：理由：胸腺基质淋巴细胞生成素（TSLP）被认为是激活树突状细胞和T细胞产生哮喘样Th炎症的枢纽细胞因子。病毒刺激是哮喘急性发作的主要原因，已显示可诱导哮喘上皮细胞TSLP的过度表达。辣椒素具有多种作用，因此很受关注，因为它使人的小气道放松。在这里，我们探讨了辣椒素对健康和哮喘供体的人支气管上皮细胞（HBEC）中病毒替代（dsRNA）诱导的TSLP和其他细胞因子（TNF-alpha，IL-8）的影响。方法：从健康和哮喘受试者获得的HBEC生长并用dsRNA刺激。还用卡塞平（3-30μM），地塞米松（0.1-10μM）或IkappaB激酶抑制剂（PS1145，30μM）预处理的细胞也暴露于dsRNA（10 mug / ml）。收获细胞和上清液用于基因表达（RT-qPCR）和蛋白质产生（ELISA，Western blot）的分析。结果：dsRNA诱导的哮喘和非哮喘性HBEC中的TSLP，TNF-α和IL-8。地塞米松减弱基因表达和蛋白质释放，而辣椒素剂量依赖性且与非松弛性NFkB抑制剂（PS1145）相似，在健康和哮喘性HBEC中完全抑制dsRNA诱导的TSLP和TNF-α。辣椒素减少了dsRNA诱导的IL-8，并阻止了dsRNA诱导的NF-κB阻遏蛋白IkBalpha的丢失。结论：除人类小气道舒张作用外，我们现在证明，辣椒素对健康和哮喘供体的HBEC中病毒刺激诱导的细胞因子具有有效的抗炎作用。基于这些数据，我们建议探索多面辣椒素中的结构活性，以寻找对病毒诱导的类固醇耐药性哮喘具有治疗价值的化合物。

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