ArticleInvestigative ophthalmology & visual science2015
Inflammasomes Induced by 7-Ketocholesterol and Other Stimuli in RPE and in Bone Marrow-Derived Cells Differ Markedly in Their Production of IL-1β and IL-18.
Article in Investigative ophthalmology & visual science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Is oxysterol accumulation a central physiological trigger of inflammaging?The Journal of physiology · 2026Article
- TREM2 in age-related macular degeneration: a microglia-centered perspective in the retinal myeloid landscape.Frontiers in ophthalmology · 2026Review
- Cholesterol-mediated inflammation activation in alveolar macrophages.BMC biology · 2025Article
- New Clues to the Pathogenesis of Idiopathic Orbital Inflammation: Elevated IL-8 and MCP-1 in Tear Fluid.Journal of ophthalmology · 2025Article
- The contribution of pattern recognition receptor signalling in the development of age related macular degeneration: the role of toll-like-receptors and the NLRP3-inflammasome.Journal of neuroinflammation · 2024Review
- Role of Oxysterols in Ocular Degeneration Mechanisms and Involvement of P2X7 Receptor.Advances in experimental medicine and biology · 2024Article
- Oxysterols as Biomarkers of Aging and Disease.Advances in experimental medicine and biology · 2024Article
- Targeting 7KCh-Induced Cell Death Response Mediated by p38, P2X7 and GSDME in Retinal Pigment Epithelium Cells with Sterculic Acid.Pharmaceutics · 2023Article
- Identification of 7-Ketocholesterol-Modulated Pathways and Sterculic Acid Protective Effect in Retinal Pigmented Epithelium Cells by Using Genome-Wide Transcriptomic Analysis.International journal of molecular sciences · 2023Article
- Immunometabolic rewiring of tubular epithelial cells in kidney disease.Nature reviews. Nephrology · 2022Review
- Gene Delivery of a Caspase Activation and Recruitment Domain Improves Retinal Pigment Epithelial Function and Modulates Inflammation in a Mouse Model with Features of Dry Age-Related Macular Degeneration.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2022Article
- Anti-inflammatory activity of date palm seed by downregulating interleukin-1β, TGF-β, cyclooxygenase-1 and -2: A study among middle age women.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2020Article
- UV-B-Induced Inflammasome Activation Can Be Prevented by Cis-Urocanic Acid in Human Corneal Epithelial Cells.Investigative ophthalmology & visual science · 2020Article
- Reversal of Endothelial Extracellular Vesicle-Induced Smooth Muscle Phenotype Transition by Hypercholesterolemia Stimulation: Role of NLRP3 Inflammasome Activation.Frontiers in cell and developmental biology · 2020Article
- Oxidized cholesterol species as signaling molecules in the brain: diabetes and Alzheimer's disease.Neuronal signaling · 2019Review
- Hypoxic expression of NLRP3 and VEGF in cultured retinal pigment epithelial cells: contribution of P2YPurinergic signalling · 2018Article
- Hsp90 inhibition as a means to inhibit activation of the NLRP3 inflammasome.Scientific reports · 2018Article
- Issues with the Specificity of Immunological Reagents for NLRP3: Implications for Age-related Macular Degeneration.Scientific reports · 2018Article
- Friend or Foe? Resident Microglia vs Bone Marrow-Derived Microglia and Their Roles in the Retinal Degeneration.Molecular neurobiology · 2017Review
- CFH Y402H polymorphism and the complement activation product C5a: effects on NF-κB activation and inflammasome gene regulation.The British journal of ophthalmology · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe inflammatory process plays a major role in the pathogenesis of AMD, and recent data indicate the involvement of inflammasomes. Inflammasomes are intracellular structures that trigger inflammation by producing mature interleukin-(IL)-1β and IL-18. This study examined the capacity of 7-ketocholesterol (7KCh), an oxysterol that accumulates in the retinal pigmented epithelium (RPE) and choroid, to initiate inflammasome formation in RPE and bone marrow-derived cells.
methodsTested cells included fetal human RPE (fhRPE), human ARPE-19 cells, primary human brain microglia cells, and human THP-1 monocyte cells. 7-Ketocholesterol and other compounds were added to the cell cultures, and their stimulatory effects were determined by quantitative PCR and release of cytokines, measured by ELISA and Western blotting.
results7-Ketocholesterol efficiently induced inflammasome formation by all primed cell populations, but secreted cytokine levels were higher in cultures of bone marrow-derived cells (microglia and THP-1 cells) than in RPE cultures. Interestingly, inflammasomes formed in cells of the two populations differed strikingly in their preferential production of the two cytokines. Thus, whereas bone marrow-derived cells produced levels of IL-1β that were higher than those of IL-18, the opposite was found with RPE cells, which secreted higher levels of IL-18. Importantly, Western blot analysis showed that IL-18, but not IL-1β, was expressed constitutively by RPE cells.
conclusions7-Ketocholesterol efficiently stimulates inflammasome formation and is conceivably involved in the pathogenesis of AMD. In contrast to bone marrow-derived cells, RPE cells produced higher levels of IL-18 than IL-1β. Further, IL-18, a multifunctional cytokine, was expressed constitutively by RPE cells. These observations provide new information about stimuli and cells and their products assumed to be involved in the pathogenesis of AMD.
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