Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Sendai, Japan.
Antimicrob Agents Chemother. 2012 Aug;56(8):4052-61. doi: 10.1128/AAC.00259-12. Epub 2012 May 14.
Respiratory virus infections, including infections with rhinoviruses (RVs), are related to exacerbations of chronic obstructive pulmonary disease (COPD). A new quinolone antibiotic, levofloxacin (LVFX), has been used to treat bacterial infections that cause COPD exacerbations as well as bacterial infections that are secondary to viral infection in COPD patients. However, the inhibitory effects of LVFX on RV infection and RV infection-induced airway inflammation have not been studied. We examined the effects of LVFX on type 14 rhinovirus (RV14) (a major human RV) infection of human tracheal epithelial cells pretreated with LVFX. LVFX pretreatment reduced the RV14 titer, the level of cytokines in the supernatant, the amount of RV14 RNA in the cells after RV14 infection, and the cells' susceptibility to RV14 infection. LVFX pretreatment decreased the mRNA level of intercellular adhesion molecule 1 (ICAM-1), a receptor for RV14, in the cells and the concentration of the soluble form of ICAM-1 in the supernatant before RV14 infection. LVFX pretreatment also decreased the number and the fluorescence intensity of the acidic endosomes from which RV14 RNA enters the cytoplasm. LVFX pretreatment inhibited the activation of nuclear factor κB proteins, including p50 and p65, in nuclear extracts. LVFX pretreatment did not reduce the titers of RV2 (a minor human RV) but reduced the titers of RV15 (a major human RV). These results suggest that LVFX inhibits major-group rhinovirus infections in part by reducing ICAM-1 expression levels and the number of acidic endosomes. LVFX may also modulate airway inflammation in rhinoviral infections.
呼吸道病毒感染,包括鼻病毒(RV)感染,与慢性阻塞性肺疾病(COPD)恶化有关。一种新型喹诺酮类抗生素左氧氟沙星(LVFX)已被用于治疗引起 COPD 恶化的细菌感染以及 COPD 患者继发于病毒感染的细菌感染。然而,LVFX 对 RV 感染和 RV 感染诱导的气道炎症的抑制作用尚未得到研究。我们研究了 LVFX 对经 LVFX 预处理的人气管上皮细胞中 14 型鼻病毒(RV14)(一种主要的人类 RV)感染的影响。LVFX 预处理降低了 RV14 的滴度、上清液中细胞因子的水平、RV14 感染后细胞中 RV14 RNA 的量以及细胞对 RV14 感染的易感性。LVFX 预处理降低了细胞中细胞间黏附分子 1(ICAM-1)的 mRNA 水平,ICAM-1 是 RV14 的受体,在 RV14 感染前上清液中可溶性 ICAM-1 的浓度也降低了。LVFX 预处理还减少了酸性内体的数量和荧光强度,RV14 RNA 从酸性内体进入细胞质。LVFX 预处理抑制了核提取物中核因子 κB 蛋白(包括 p50 和 p65)的激活。LVFX 预处理并未降低 RV2(一种次要的人类 RV)的滴度,但降低了 RV15(一种主要的人类 RV)的滴度。这些结果表明,LVFX 通过降低 ICAM-1 表达水平和酸性内体的数量部分抑制主要组鼻病毒感染。LVFX 还可能调节呼吸道病毒感染中的气道炎症。