ArticleInvestigative ophthalmology & visual science2012
Acanthamoeba-cytopathic protein induces apoptosis and proinflammatory cytokines in human corneal epithelial cells by cPLA2α activation.
Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Oxidative Stress and Redox Imbalance inInternational journal of molecular sciences · 2026Review
- Acanthamoeba castellanii cysteine protease 3 promotes M1 macrophage polarization through the TLR4/NF‑κB pathway.Parasites & vectors · 2025Article
- Virus and cell specific HMGB1 secretion and subepithelial infiltrate formation in adenovirus keratitis.PLoS pathogens · 2025Article
- The role of apoptosis and oxidative stress in the pathophysiology of Acanthamoeba spp. infection in the kidneys of hosts with different immunological status.Parasites & vectors · 2023Article
- Article
- Quantitative proteomic analysis and functional characterization of Acanthamoeba castellanii exosome-like vesicles.Parasites & vectors · 2019Article
- Acanthamoeba Activates Macrophages Predominantly through Toll-Like Receptor 4- and MyD88-Dependent Mechanisms To Induce Interleukin-12 (IL-12) and IL-6.Infection and immunity · 2017Article
- Cytotoxic activity and degradation patterns of structural proteins by corneal isolates of Acanthamoeba spp.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2015Article
- Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells.Investigative ophthalmology & visual science · 2014Article
- Pathogenic strains of Acanthamoeba are recognized by TLR4 and initiated inflammatory responses in the cornea.PloS one · 2014Article
- Dual role of the p38 MAPK/cPLA2 pathway in the regulation of platelet apoptosis induced by ABT-737 and strong platelet agonists.Cell death & disease · 2013Article
- Role of phospholipase A₂ (PLA₂) inhibitors in attenuating apoptosis of the corneal epithelial cells and mitigation of Acanthamoeba keratitis.Experimental eye research · 2013Article
- Significance of arachidonic acid in ocular infections and inflammation.Inflammation and cell signalingArticle
- Role of protease-activated receptors 2 (PAR2) in ocular infections and inflammation.Receptors & clinical investigationArticle
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4 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeWe have shown that Acanthamoeba interacts with a mannosylated protein on corneal epithelial cells and stimulates trophozoites to secrete a mannose-induced 133 kDa protease (MIP-133), which facilitates corneal invasion and induces apoptosis. The mechanism of MIP-133-induced apoptosis is unknown. The aim of this study was to determine if MIP-133 induces apoptosis and proinflammatory cytokines/chemokines in human corneal epithelial (HCE) cells via the cytosolic phospholipase A(2α) (cPLA(2α)) pathway.
methodsHCE cells were incubated with or without MIP-133 at doses of 7.5, 15, and 50 μg/mL for 6, 12, and 24 hours. The effects of cPLA(2α) inhibitors on cPLA(2α), arachidonic acid (AA) release, and apoptosis were tested in vitro. Inhibition of cPLA(2α) involved preincubating HCE cells for 1 hour with cPLA(2α) inhibitors (10 μM methyl-arachidonyl fluorophosphonate [MAFP] or 20 μM arachidonyl trifluoromethyl ketone [AACOCF3]) with or without MIP-133 for 24 hours. Expression of cPLA(2α) mRNA and enzyme was examined by RT-PCR and cPLA(2) activity assays, respectively. Apoptosis of corneal epithelial cells was determined by caspase-3 and DNA fragmentation assays. Expression of IL-8, IL-6, IL-1β, and IFN-γ was examined by RT-PCR and ELISA.
resultsMIP-133 induced significant cPLA(2α) (approximately two to four times) and AA release (approximately six times) from corneal cells while cPLA(2α) inhibitors significantly reduced cPLA(2α) (approximately two to four times) and AA release (approximately three times) (P < 0.05). cPLA(2α) inhibitors significantly inhibited MIP-133-induced DNA fragmentation approximately 7 to 12 times in HCE cells (P < 0.05). MIP-133 specifically activates cPLA(2α) enzyme activity in HCE cells, which is blocked by preincubation with anti-MIP-133 antibody. In addition, MIP-133 induced significant IL-8, IL-6, IL-1β, and IFN-γ production, approximately two to three times (P < 0.05).
conclusionsMIP-133 interacts with phospholipids on plasma membrane of HCE cells and activates cPLA(2α). cPLA(2α) is involved in apoptosis, AA release, and activation of proinflammatory cytokines/chemokines from HCE cells. cPLA(2α) inhibitors may be a therapeutic target in Acanthamoeba keratitis.
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