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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.
Eur J Nutr. 2010 Oct; 49(7):435-46.EJ

Abstract

BACKGROUND AND AIMS

Oxysterols 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.

METHODS

ARPE-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.

RESULTS

7β-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.

CONCLUSION

7β-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.

Authors+Show Affiliations

Université de Bourgogne and INSERM 866, Faculté des Sciences Gabriel, 21000 Dijon, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20339855

Citation

Dugas, B, et al. "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." European Journal of Nutrition, vol. 49, no. 7, 2010, pp. 435-46.
Dugas B, Charbonnier S, Baarine M, et al. 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. Eur J Nutr. 2010;49(7):435-46.
Dugas, B., Charbonnier, S., Baarine, M., Ragot, K., Delmas, D., Ménétrier, F., Lherminier, J., Malvitte, L., Khalfaoui, T., Bron, A., Creuzot-Garcher, C., Latruffe, N., & Lizard, G. (2010). 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. European Journal of Nutrition, 49(7), 435-46. https://doi.org/10.1007/s00394-010-0102-2
Dugas B, et al. 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. Eur J Nutr. 2010;49(7):435-46. PubMed PMID: 20339855.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Dugas,B, AU - Charbonnier,S, AU - Baarine,M, AU - Ragot,K, AU - Delmas,D, AU - Ménétrier,F, AU - Lherminier,J, AU - Malvitte,L, AU - Khalfaoui,T, AU - Bron,A, AU - Creuzot-Garcher,C, AU - Latruffe,N, AU - Lizard,Gérard, Y1 - 2010/03/27/ PY - 2009/12/03/received PY - 2010/03/08/accepted PY - 2010/3/27/entrez PY - 2010/3/27/pubmed PY - 2011/1/5/medline SP - 435 EP - 46 JF - European journal of nutrition JO - Eur J Nutr VL - 49 IS - 7 N2 - BACKGROUND AND AIMS: Oxysterols 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. METHODS: ARPE-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. RESULTS: 7β-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. CONCLUSION: 7β-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. SN - 1436-6215 UR - https://www.unboundmedicine.com/medline/citation/20339855/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_ L2 - https://dx.doi.org/10.1007/s00394-010-0102-2 DB - PRIME DP - Unbound Medicine ER -