Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Clinical Research Institute, Daejeon St Mary's Hospital, Daejeon, Republic of Korea.
Int Forum Allergy Rhinol. 2019 Jun;9(6):638-647. doi: 10.1002/alr.22296. Epub 2019 Feb 13.
Exposure to urban particulate matter (UPM) has been studied as a cause of various health problems. Although the association between UPM and the respiratory tract has been well studied, further research is required to characterize the effects of UPM on the upper respiratory tract. We investigated the effects of UPM-induced reactive oxygen species (ROS) production on cultured human nasal fibroblasts, as well as the protective effects of α-lipoic acid (ALA) on ROS production and the underlying signaling pathways involved in ROS inhibition.
Human turbinate tissue specimens were collected from 6 patients. The effects of UPM on the viability of cultured nasal fibroblasts were determined. A fluorescent malondialdehyde assay was used to measure ROS levels. Real-time reverse transcription polymerase chain reaction was used to measure the messenger RNA levels of genes encoding Nrf2, the antioxidant response elements (AREs) (HO-1, NQO1), and the proinflammatory cytokines (interleukin-6 and interleukin-8) before and after ALA treatment. Western blotting analyses were used to measure nuclear and cytosolic Nrf2 and AREs.
UPM reduced cell viability and increased ROS expression in nasal fibroblasts. ALA treatment decreased ROS production in UPM-exposed fibroblasts via the Nrf2, HO-1, and NQO-1 pathways. Also, ALA treatment abrogated increases in the interleukin-6 and -8 levels induced by UPM in nasal fibroblasts.
UPM exposure resulted in increased ROS production in nasal fibroblasts. ALA treatment inhibited this increase via the Nrf2 pathway, suggesting that ALA may have a protective effect against rhinitis caused by ROS expression induced by exposure to UPM.
已有研究表明,接触城市颗粒物(UPM)是引发各种健康问题的原因之一。尽管 UPM 与呼吸道之间的关联已得到充分研究,但仍需要进一步研究以表征 UPM 对上呼吸道的影响。我们研究了 UPM 诱导的活性氧(ROS)产生对培养的人鼻腔成纤维细胞的影响,以及α-硫辛酸(ALA)对 ROS 产生的保护作用及其对 ROS 抑制相关信号通路的影响。
从 6 名患者中采集鼻甲组织标本。测定 UPM 对培养的鼻成纤维细胞活力的影响。采用荧光丙二醛测定法测定 ROS 水平。实时逆转录聚合酶链反应(RT-PCR)测定 ALA 处理前后编码 Nrf2 的基因、抗氧化反应元件(AREs)(HO-1、NQO1)和促炎细胞因子(白细胞介素-6 和白细胞介素-8)的信使 RNA 水平。Western blot 分析用于测定核和胞质 Nrf2 和 AREs。
UPM 降低了鼻成纤维细胞的活力并增加了 ROS 的表达。ALA 处理通过 Nrf2、HO-1 和 NQO1 途径降低了 UPM 暴露的成纤维细胞中的 ROS 产生。此外,ALA 处理阻断了 UPM 诱导的鼻成纤维细胞中白细胞介素-6 和白细胞介素-8 水平的升高。
UPM 暴露导致鼻成纤维细胞中 ROS 产生增加。ALA 处理通过 Nrf2 途径抑制了这种增加,表明 ALA 可能对 UPM 诱导的 ROS 表达引起的鼻炎具有保护作用。