1. Role of phospholipase A₂ (PLA₂) inhibitors in attenuating apoptosis of the corneal epithelial cells and mitigation of Acanthamoeba keratitis.
- Author
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Tripathi T, Abdi M, and Alizadeh H
- Subjects
- Acanthamoeba Keratitis etiology, Acanthamoeba Keratitis pathology, Acanthamoeba castellanii drug effects, Animals, Arachidonic Acids metabolism, Arachidonic Acids pharmacology, Blotting, Western, Cells, Cultured, Chemokine CXCL2 metabolism, Chromatography, High Pressure Liquid, Conjunctiva drug effects, Conjunctiva metabolism, Cricetinae, Cricetulus, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Mannose metabolism, Organophosphonates pharmacology, Phospholipases A2, Cytosolic genetics, Phospholipases A2, Cytosolic metabolism, Protozoan Proteins pharmacology, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Up-Regulation, Acanthamoeba Keratitis prevention & control, Apoptosis drug effects, Enzyme Inhibitors pharmacology, Epithelium, Corneal pathology, Phospholipases A2, Cytosolic antagonists & inhibitors
- Abstract
The aim of this study is to determine if the mannose-induced protein (MIP-133) from Acanthamoeba castellanii trophozoites induces apoptosis of corneal epithelial cells through a cytosolic phospholipase A2α (cPLA2α)-mediated pathway. The efficacy of cPLA2α inhibitors to provide protection against Acanthamoeba keratitis was examined in vivo. Chinese hamster corneal epithelial (HCORN) cells were incubated with or without MIP-133. MIP-133 induces significant increase in cPLA2α and macrophage inflammatory protein-2 (MIP-2/CXCL2) levels from corneal cells. Moreover, cPLA2α inhibitors, MAFP (Methyl-arachidonyl fluorophosphonate) and AACOCF3 (Arachidonyl trifluoromethyl ketone), significantly reduce cPLA2α and CXCL2 from these cells (P < 0.05). Additionally, cPLA2α inhibitors significantly inhibit MIP-133-induced apoptosis in HCORN cells (P < 0.05). Subconjunctival injection of purified MIP-133 in Chinese hamster eyes induced cytopathic effects resulting in corneal ulceration. Animals infected with A. castellanii-laden contact lenses and treated with AACOCF3 and CAY10650, showed significantly less severe keratitis as compared with control animals. Collectively, the results indicate that cPLA2α is involved in MIP-133 induced apoptosis of corneal epithelial cells, polymorphonuclear neutrophil infiltration, and production of CXCL2. Moreover, cPLA2α inhibitors can be used as a therapeutic target in Acanthamoeba keratitis., (Copyright © 2013. Published by Elsevier Ltd.)
- Published
- 2013
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