The Institute of Vision Research, Department of Ophthalmology, and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
Free Radic Biol Med. 2013 Oct;63:78-89. doi: 10.1016/j.freeradbiomed.2013.05.006. Epub 2013 May 9.
Changes in the ocular surface induced by ozone have received limited research attention. Here, we investigate the effects of ozone exposure on the integrity of the ocular surface, the production of inflammatory cytokines in tears, and changes in mucin-secreting cells in a mouse model. In addition, ozone-induced nuclear factor-κB (NF-κB)-mediated inflammatory processes were evaluated in cultured human conjunctival epithelial cells. In vivo, ozone induced the breakdown of corneal epithelial integrity, decreased the number of mucin-secreting cells, and induced the production of inflammatory cytokines, without altering tear volume. In vitro, ozone exposure led to increases in NF-κB nuclear translocation, κB-dependent transcriptional activity, NF-κB inhibitor α (IκBα) proteolysis, and expression of phosphorylated IκBα (p-IκBα), but did not cause cytotoxicity or cellular apoptosis. In addition, ozone induced the expression of inflammatory cytokines, Toll-like receptors, and C-C chemokine receptors, but decreased the expression of mucins. Furthermore, inhibition of NF-κB with pyrrolidine dithiocarbamate before exposure of cultured human conjunctival epithelial cells to ozone prevented changes in IκBα and p-IκBα levels in association with a decrease in the levels of inflammatory cytokines. Therefore, we conclude that ozone exposure interferes with ocular surface integrity and induces inflammation involving NF-κB-mediated processes at the level (and/or upstream) of IκBα. Understanding the role of ozone in the initiation of inflammatory processes on the animal ocular surface and in cultured human conjunctival epithelial cells can help elucidate the pathogenesis of ocular surface damage and suggest protective strategies for preserving a healthy ocular surface against ozone exposure.
臭氧对眼表的影响引起了人们的关注。本研究旨在观察臭氧暴露对眼表完整性、泪液中炎症细胞因子产生以及粘蛋白分泌细胞变化的影响，并评估臭氧诱导的核因子-κB（NF-κB）介导的炎症反应在培养的人结膜上皮细胞中的作用。体内实验中，臭氧诱导角膜上皮完整性破坏，粘蛋白分泌细胞减少，炎症细胞因子产生增加，而泪液量无变化。体外实验中，臭氧暴露导致 NF-κB 核易位、κB 依赖性转录活性、NF-κB 抑制剂α（IκBα）的蛋白水解以及磷酸化 IκBα（p-IκBα）的表达增加，但不引起细胞毒性或细胞凋亡。此外，臭氧诱导炎症细胞因子、Toll 样受体和 C-C 趋化因子受体的表达减少，粘蛋白的表达降低。用吡咯烷二硫代氨基甲酸盐（NF-κB 抑制剂）预处理培养的人结膜上皮细胞，可抑制臭氧诱导的 IκBα和 p-IκBα水平变化，并降低炎症细胞因子水平。因此，我们得出结论，臭氧暴露破坏眼表完整性，并诱导 NF-κB 介导的炎症反应，该反应可能涉及 IκBα 水平（和/或上游）的改变。了解臭氧在动物眼表和培养的人结膜上皮细胞中引发炎症反应的作用，有助于阐明眼表损伤的发病机制，并为保护眼表免受臭氧暴露提供策略。
