title: Effects of ozone exposure on the ocular surface.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hun
authors.initials: H
authors.lastname: Lee
authors.forename: Eung Kweon
authors.initials: EK
authors.lastname: Kim
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Kang
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Hwang
authors.forename: Tae-Im
authors.initials: TI
authors.lastname: Kim
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005123:Eye / Q000187:drug effects*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009799:Ocular Physiological Phenomena / Q000187:drug effects / Q000235:genetics; D010126:Ozone / Q000008:administration & dosage*; D010766:Phosphorylation; D013499:Surface Properties / Q000187:drug effects; D013666:Tears / Q000187:drug effects / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D016207:Cytokines; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D010126:Ozone
keywords: Free radicals; Mucin-secreting cell; NF-κB; Ocular surface integrity; Ozone; Pyrrolidine dithiocarbamate; Tear cytokines