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Provedor de dados:  Inra
País:  France
Título:  Effects of oxysterols on cell viability, inflammatory cytokines, VEGF, and reactive oxygen species production on human retinal cells: cytoprotective effects and prevention of VEGF secretion by resveratrol
Autores:  Dugas, B.
Charbonnier, S.
Baarine, M.
Ragot, K.
Delmas, D.
Menetrier, F.
Lherminier, J.
Malvitte, L.
Khalfaoui, T.
Bron, A.
Creuzot Garcher, C.
Latruffe, N.
Lizard, G.
Data:  2010
Ano:  2010
Palavras-chave:  CELLULES RÉTINIENNES
DEGENERESCENCE MACULAIRE
DMLA ARPE-19 CELLS
CASPASE-INDEPENDENT CELL DEATH
INFLAMMATORY CYTOKINES
OXYSTEROLS
PHOSPHOLIPIDOSIS
RESVERATROL
REACTIVE OXYGEN SPECIES
VEGF
Resumo:  Background and aimsOxysterols are assumed to play important roles in age-related macular degeneration, a major cause of blindness. So we characterized the cytotoxic, oxidative, inflammatory, and angiogenic activities of oxysterols (7β-hydroxycholesterol (7β-OH), 7-ketocholesterol (7KC), 25-hydroxycholesterol (25-OH)) in human retinal ARPE-19 cells, and evaluated the protective effects of resveratrol (Rsv: 1 μM), a polyphenol from red wine.MethodsARPE-19 cells were treated with 7β-OH, 7KC, or 25-OH (5–40 μg/mL; 24–48 h) without or with Rsv. Cell viability was determined using trypan blue and the MTT assay. Cell death was characterized by electron microscopy and in situ detection of activated caspases with fluorochrome-labeled inhibitors of caspases. Reactive oxygen species (ROS) production was measured with hydroethidine. ELISA methods and a cytometric bead assay were used to quantify cytokines involved in inflammation (IL-8, IL-1β, IL-6, IL-10, IL-12p70, TNF-α, MCP-1) and VEGF.Results7β-OH and 7KC triggered a caspase-independent cell death process associated with the presence of multilamellar cytoplasmic structures evocating phospholipidosis, increased ROS production, and IL-8 secretion. 7β-OH enhanced VEGF secretion. No cytotoxic effects were identified with 25-OH, which highly stimulated ROS production, MCP-1, and VEGF secretion. With oxysterols, no IL-10, TNF-α, and IL-12p70 secretion were detected. 25-OH induced IL-8 secretion through the MEK/ERK½ signaling pathway, and Rsv showed cytoprotective activities and inhibited VEGF secretion.Conclusion7β-OH, 7KC, and 25-OH have cytotoxic, oxidative, inflammatory, and/or angiogenic activities on ARPE-19 cells. As Rsv has some protective effects against oxysterol-induced cell death and VEGF secretion it could be valuable in ARMD treatment.
Tipo:  Journal Article
Idioma:  Inglês
Identificador:  http://www.prodinra.inra.fr/prodinra/pinra/doc.xsp?id=PROD201135a1139e&uri=/notices/prodinra1/2011/06/
Fonte:  European Journal of Nutrition. 2010, 49 (7) : 435-446
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