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 a (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.
|Number of pages||12|
|Journal||Free Radical Biology and Medicine|
|State||Published - 2013|
Bibliographical noteFunding Information:
This study was supported by grant MEST (2010-0022006) from the National Research Foundation of Korea and the Converging Research Center Program funded by the Ministry of Education, Science and Technology (2012K001354). We thank Dong-Su Jang for his excellent support with medical illustration and Yura Shin from Hankuk Academy of Foreign Studies for her help with the data analysis and correction of English in the study.
- Free radicals
- Mucin-secreting cell
- Ocular surface integrity
- Pyrrolidine dithiocarbamate
- Tear cytokines