Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients.
Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients.
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DOI：
10.1038/srep28698
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发表时间：
2016-06-28
影响因子：
4.6
通讯作者：
Uller L
中科院分区：
文献类型：
--
作者：
Menzel M;Akbarshahi H;Bjermer L;Uller L
鼻病毒感染是慢性阻塞性肺病（COPD）恶化的主要原因，并可能导致 COPD 发展为严重阶段。大环内酯类抗生素阿奇霉素可能具有抗病毒作用，据报道可以减少慢性阻塞性肺病的恶化。然而，人们对其在临床相关浓度下对支气管上皮细胞的抗病毒作用知之甚少。来自 COPD 供体和健康个体的原代支气管上皮细胞在感染鼻病毒 RV16 前 24 小时开始连续使用阿奇霉素治疗。分析了干扰素、RIG-I 样解旋酶、促炎细胞因子和病毒载量的表达。阿奇霉素短暂增加未感染 COPD 细胞中 IFNβ 和 IFNλ1 以及 RIG-I 样解旋酶的表达。此外，阿奇霉素在 COPD 细胞中增强了 RV16 诱导的干扰素和 RIG-I 样解旋酶的表达，但在健康上皮细胞中却没有增强。阿奇霉素还可以降低病毒载量。然而，它仅适度改变 RV16 诱导的促炎细胞因子表达。添加布地奈德并不会降低阿奇霉素的干扰素诱导作用。阿奇霉素可能通过诱导 RIG-I 样解旋酶的表达，增加了 COPD 中鼻病毒诱导的干扰素表达，但在健康支气管上皮中却没有增加。这些作用将减少支气管病毒载量，支持阿奇霉素在预防慢性阻塞性肺病恶化方面的新作用。
Rhinovirus infection is a major cause of chronic obstructive pulmonary disease (COPD) exacerbations and may contribute to the development into severe stages of COPD. The macrolide antibiotic azithromycin may exert anti-viral actions and has been reported to reduce exacerbations in COPD. However, little is known about its anti-viral actions on bronchial epithelial cells at clinically relevant concentrations. Primary bronchial epithelial cells from COPD donors and healthy individuals were treated continuously with azithromycin starting 24 h before infection with rhinovirus RV16. Expression of interferons, RIG-I like helicases, pro-inflammatory cytokines and viral load were analysed. Azithromycin transiently increased expression of IFNβ and IFNλ1 and RIG-I like helicases in un-infected COPD cells. Further, azithromycin augmented RV16-induced expression of interferons and RIG-I like helicases in COPD cells but not in healthy epithelial cells. Azithromycin also decreased viral load. However, it only modestly altered RV16-induced pro-inflammatory cytokine expression. Adding budesonide did not reduce interferon-inducing effects of azithromycin. Possibly by inducing expression of RIG-I like helicases, azithromycin increased rhinovirus-induced expression of interferons in COPD but not in healthy bronchial epithelium. These effects would reduce bronchial viral load, supporting azithromycin’s emerging role in prevention of exacerbations of COPD.