Inflammasomes Induced by 7-Ketocholesterol and Other Stimuli in RPE and in Bone Marrow-Derived Cells Differ Markedly in Their Production of IL-1 and IL-18
| Autor: | Osato Ogbeifun, Samuel J. H. Hinshaw, Lindsey F. Nugent, Ignacio R. Rodriguez, Igal Gery, Siqi Chen, Wambui S. Wandu, Arvydas Maminishkis, Guangpu Shi |
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| Rok vydání: | 2015 |
| Předmět: |
Inflammasomes
medicine.medical_treatment Blotting Western Interleukin-1beta Bone Marrow Cells Enzyme-Linked Immunosorbent Assay Inflammation Retinal Pigment Epithelium Biology Cellular and Molecular Neuroscience medicine Humans Ketocholesterols Cells Cultured Retinal pigment epithelium Microglia Monocyte Interleukin-18 Inflammasome Articles eye diseases Sensory Systems Cell biology Ophthalmology medicine.anatomical_structure Cytokine Cell culture Immunology sense organs Bone marrow medicine.symptom medicine.drug |
| Zdroj: | Investigative Ophthalmology & Visual Science. 56:1658-1664 |
| ISSN: | 0146-0404 |
| Popis: | PURPOSE The 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. METHODS Tested 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. RESULTS 7-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. CONCLUSIONS 7-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. |
| Databáze: | OpenAIRE |
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