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丙酸氟替卡松和沙美特罗对抑制鼻病毒诱导的上皮细胞产生重塑相关生长因子的协同作用。

Synergistic effects of fluticasone propionate and salmeterol on inhibiting rhinovirus-induced epithelial production of remodelling-associated growth factors.

作者信息

Volonaki E, Psarras S, Xepapadaki P, Psomali D, Gourgiotis D, Papadopoulos N G

机构信息

Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece.

出版信息

Clin Exp Allergy. 2006 Oct;36(10):1268-73. doi: 10.1111/j.1365-2222.2006.02566.x.

DOI:10.1111/j.1365-2222.2006.02566.x
PMID:17014435
Abstract

BACKGROUND

Rhinoviruses (RV), the major trigger of acute asthma exacerbations, are able to infect bronchial epithelium and induce production of pro-inflammatory, but also angiogenic and pro-fibrotic mediators. Fluticasone propionate (FP) and salmeterol (S) are clinically effective and act synergistically in controlling persistent asthma; however, their effect on virus-associated asthma is less clear.

AIM

The aim of this study was to assess the individual and combined effects of FP and S on RV-induced epithelial production of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2).

METHODS

Bronchial epithelial cells (BEAS-2B) were exposed in vitro to RV and were subsequently treated with FP and S, at physiologically relevant concentrations, alone or in combination. VEGF and FGF-2 were measured in the supernatants of these cultures using ELISA.

RESULTS

FP was able to reduce RV-induced VEGF production in a dose-dependent manner. S also induced a smaller reduction; addition of both factors inhibited VEGF synergistically. FGF-2 production was not inhibited by either FP or S alone, but was significantly reduced when both substances were present in the culture.

CONCLUSION

This study demonstrates that FP and S may synergistically inhibit the production of angiogenic and/or pro-fibrotic factors that are induced after RV infection of BEAS-2B and are implicated in airway remodelling, suggesting that this combination may represent an important therapeutic option on virus-induced asthma.

摘要

背景

鼻病毒(RV)是急性哮喘发作的主要诱因,能够感染支气管上皮并诱导促炎介质以及血管生成和促纤维化介质的产生。丙酸氟替卡松(FP)和沙美特罗(S)在临床上对控制持续性哮喘有效且具有协同作用;然而,它们对病毒相关性哮喘的影响尚不清楚。

目的

本研究旨在评估FP和S对RV诱导的上皮细胞产生血管内皮生长因子(VEGF)和成纤维细胞生长因子-2(FGF-2)的单独及联合作用。

方法

体外将支气管上皮细胞(BEAS-2B)暴露于RV,随后用生理相关浓度的FP和S单独或联合处理。使用酶联免疫吸附测定法(ELISA)测量这些培养物上清液中的VEGF和FGF-2。

结果

FP能够以剂量依赖的方式降低RV诱导的VEGF产生。S也能诱导较小程度的降低;两种因子联合使用时可协同抑制VEGF。单独使用FP或S均不能抑制FGF-2的产生,但当两种物质同时存在于培养物中时,FGF-2的产生显著降低。

结论

本研究表明,FP和S可能协同抑制BEAS-2B受到RV感染后诱导产生的、与气道重塑有关的血管生成和/或促纤维化因子的产生,这表明该联合用药可能是病毒诱导性哮喘的一种重要治疗选择。

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