Abstract
It is generally accepted that high osmotic pressure (HOP) of lacrimal fluid is the core mechanism causing ocular inflammation and injury. However, the association between HOP and the regulation of cell inflammatory response and apoptotic pathways remains unclear. In the present study, we used HOP to interfere with in vitro cultured rabbit corneal epithelial cells, and found that HOP increased the generation of reactive oxygen species (ROS) in rabbit corneal epithelial cells, and increased ROS in turn induced the activation of JNK inflammatory signaling pathway, which further promoted the expression of pro-inflammatory factor NF-κβ and induced the generation of inflammatory factor IL-1β and TNF-α. In addition, HOP-induced ROS in rabbit corneal epithelial cells regulated the CD95/CD95L-mediated cell apoptotic signaling pathway by activating JNK inflammatory signaling pathway. These findings may serve as new theoretical basis and a new way of thinking about the treatment of ocular diseases, especially dry eye.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Annexin A5 / metabolism
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Apoptosis*
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Cells, Cultured
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Culture Media
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Enzyme-Linked Immunosorbent Assay
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Epithelial Cells / metabolism*
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Epithelial Cells / pathology*
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Epithelium, Corneal / pathology*
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Fas Ligand Protein / metabolism
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Flow Cytometry
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Gene Expression Regulation
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Interleukin-1beta / metabolism
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JNK Mitogen-Activated Protein Kinases / metabolism
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NF-kappa B / metabolism
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Osmotic Pressure*
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Phosphorylation
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Rabbits
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Reactive Oxygen Species / metabolism*
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Signal Transduction*
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
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fas Receptor / metabolism
Substances
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Annexin A5
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Culture Media
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Fas Ligand Protein
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Interleukin-1beta
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NF-kappa B
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Reactive Oxygen Species
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Tumor Necrosis Factor-alpha
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fas Receptor
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JNK Mitogen-Activated Protein Kinases
Grants and funding
This work was supported by grants from the Natural Science Foundation of Shanghai (No. 11ZR1427900); the Youth Research Project of Shanghai Municipal Health Bureau(No. 2010Y164); the Young Talent Training Plan of Tongji University(No. 2010KJ018); the Young Talent Training Plan of Shanghai Tenth PeopleShanghai Tenth People?? Hospital (No. 11RQ108); Shanghai Health Hospital Development Center Foundation Project (SHDC12007104). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.