Alves Marco P, Schögler Aline, Ebener Simone, Vielle Nathalie J, Casaulta Carmen, Jung Andreas, Moeller Alexander, Geiser Thomas, Regamey Nicolas
Department of Clinical Research, University Hospital of Bern, Bern, Switzerland.
Division of Pediatric Respiratory Medicine, University Children's Hospital, Bern, Switzerland.
Respirology. 2016 Feb;21(2):304-12. doi: 10.1111/resp.12692. Epub 2015 Nov 26.
Rhinoviruses (RV) replicate in both upper and lower airway epithelial cells. We evaluated the possibility of using nasal epithelial cells (NEC) as surrogate of bronchial epithelial cells (BEC) for RV pathogenesis cell culture studies.
We used primary paired NEC and BEC cultures established from healthy subjects and compared the replication of RV belonging to the major (RV16) and minor (RV1B) group, and the cellular antiviral and proinflammatory cytokine responses towards these viruses. We related antiviral and pro-inflammatory responses of NEC isolated from CF and COPD patients with those of BEC.
RV16 replication and major group surface receptor (ICAM-1) expression were higher in healthy NEC compared with BEC (P < 0.05); RV1B replication and minor group surface receptor (LDLR) expression were similar. Healthy NEC and BEC produced similar levels of IFN-β and IFN-λ2/3 upon RV infection or after simulation with poly(IC). IL-8 production was similar between healthy NEC and BEC. IL-6 release at baseline (P < 0.01) and upon infection with RV16 (P < 0.05) and poly(IC) stimulation (P < 0.05) was higher in NEC. RV1B viral load in NEC was related to RV1B viral load in BEC (r = 0.49, P = 0.01). There was a good correlation of IFN levels between NEC and BEC (r = 0.66, P = 0.0004 after RV1B infection). IL-8 production in NEC was related to IL-8 production in BEC (r = 0.48, P = 0.02 after RV1B infection).
NEC are a suitable alternative cellular system to BEC to study the pathophysiology of RV infections and particularly to investigate IFN responses induced by RV infection.
鼻病毒（RV）可在上、下呼吸道上皮细胞中复制。我们评估了在RV发病机制细胞培养研究中，使用鼻上皮细胞（NEC）作为支气管上皮细胞（BEC）替代物的可能性。
我们使用从健康受试者建立的原代配对NEC和BEC培养物，比较了主要组（RV16）和次要组（RV1B）RV的复制情况，以及细胞对这些病毒的抗病毒和促炎细胞因子反应。我们将从囊性纤维化（CF）和慢性阻塞性肺疾病（COPD）患者分离的NEC的抗病毒和促炎反应与BEC的反应进行了关联。
与BEC相比，健康NEC中RV16复制及主要组表面受体（ICAM-1）表达更高（P<0.05）；RV1B复制及次要组表面受体（LDLR）表达相似。健康NEC和BEC在RV感染后或用聚肌胞苷酸（poly(IC)）模拟后产生的IFN-β和IFN-λ2/3水平相似。健康NEC和BEC之间的IL-8产生相似。NEC在基线时（P<0.01）、感染RV16后（P<0.05）及poly(IC)刺激后（P<0.05）的IL-6释放更高。NEC中的RV1B病毒载量与BEC中的RV1B病毒载量相关（r=0.49，P=0.01）。NEC和BEC之间的IFN水平有良好相关性（RV1B感染后r=0.66，P=0.0004）。NEC中的IL-8产生与BEC中的IL-8产生相关（RV1B感染后r=0.48，P=0.02）。
NEC是BEC的合适替代细胞系统，可用于研究RV感染的病理生理学，特别是研究RV感染诱导的IFN反应。
