Department of Otorhinolaryngology, Gyeongsang National University Hospital, Jinju, Republic of Korea.
Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Am J Respir Cell Mol Biol. 2020 Jan;62(1):95-103. doi: 10.1165/rcmb.2018-0377OC.
IL-17 family cytokines are directly involved in host immune responses and the critical mediators for host defense against infection or inflammation. IL-17C is highly expressed in respiratory epithelium and is induced after acute bacterial lung infection. However, the definite function of IL-17C induced by (PAO1 strain) is not fully understood, and our study was designed to demonstrate IL-17C-induced immune response against PAO1 infection in nasal epithelium. Passage-2 normal human nasal epithelial (NHNE) cells were infected with PAO1 and the relationship between IL-17C-related immune responses and the iron absorption of PAO1, depending on inoculation of recombinant human IL-17C (rhIL-17C), was assessed by measuring the siderophore activity of PAO1. Microarray data showed that IL-17C expression increased 34.7 times at 8 hours postinfection (hpi) in NHNE cells, and IL-17C mRNA levels increased until 48 hpi. The PAO1 colonies significantly increased from 8 hpi in NHNE cells, and siderophore activity of PAO1 was enhanced in the supernatants of PAO1-infected NHNE cells. Interestingly, PAO1 colonies were reduced in PAO1-infected NHNE cells treated with rhIL-17C, and supernatants from NHNE cells treated with rhIL-17C also exhibited decreased PAO1 colonies. We found that the siderophore activity of PAO1 was significantly reduced in the supernatants of NHNE cells treated with rhIL-17C where LCN2 expression was highly elevated. Our findings indicate that IL-17C mediates an antibacterial effect against PAO1 by inhibiting siderophore activity in nasal epithelium. We propose that IL-17C might be an efficient mediator to suppress PAO1 infection through disturbing iron absorption of PAO1 in nasal epithelium.
白细胞介素-17 家族细胞因子直接参与宿主免疫反应，是宿主防御感染或炎症的关键介质。白细胞介素-17C 在呼吸道上皮细胞中高度表达，并在急性细菌性肺感染后被诱导。然而， （PAO1 株）诱导的白细胞介素-17C 的明确功能尚未完全了解，我们的研究旨在证明鼻上皮细胞中白细胞介素-17C 诱导的免疫反应对 PAO1 感染的作用。将第二代正常人体鼻上皮（NHNE）细胞用 PAO1 感染，通过测量 PAO1 的铁吸收情况来评估与白细胞介素-17C 相关的免疫反应与 PAO1 的铁吸收之间的关系，接种重组人白细胞介素-17C（rhIL-17C）。微阵列数据显示，感染后 8 小时 NHNE 细胞中白细胞介素-17C 的表达增加了 34.7 倍，IL-17C mRNA 水平一直增加到 48 小时。PAO1 菌落从感染后 8 小时开始在 NHNE 细胞中显著增加，PAO1 感染 NHNE 细胞上清液中的铁载体活性增强。有趣的是，用 rhIL-17C 处理 PAO1 感染的 NHNE 细胞后，PAO1 菌落减少，用 rhIL-17C 处理的 NHNE 细胞上清液也显示出减少的 PAO1 菌落。我们发现，在 rhIL-17C 处理的 NHNE 细胞上清液中，LCN2 表达高度升高，PAO1 的铁载体活性显著降低。我们的研究结果表明，白细胞介素-17C 通过抑制鼻上皮细胞中的铁载体活性，介导针对 PAO1 的抗菌作用。我们提出，白细胞介素-17C 可能通过干扰 PAO1 在鼻上皮细胞中的铁吸收，成为抑制 PAO1 感染的有效介质。
