Differential Expression of Inflammasome-Related Genes in Induced Pluripotent Stem-Cell-Derived Retinal Pigment Epithelial Cells with or without History of Age-Related Macular Degeneration

Autor:	Hytti, Maria, Korhonen, Eveliina, Hongisto, Heidi, Kaarniranta, Kai, Skottman, Heli, Kauppinen, Anu
Přispěvatelé:	Tampere University, BioMediTech
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	QH301-705.5 induced pluripotent stem cells Inflammasomes Gene Expression Profiling retinal pigment epithelium Epithelial Cells eye diseases Article Cell Line Chemistry Macular Degeneration Gene Expression Regulation inflammation Cytokines Humans 3111 Biomedicine sense organs Disease Susceptibility HSP90 Heat-Shock Proteins Biology (General) Inflammation Mediators QD1-999 age-related macular degeneration Biomarkers Cells Cultured
Zdroj:	International Journal of Molecular Sciences Volume 22 Issue 13 International Journal of Molecular Sciences, Vol 22, Iss 6800, p 6800 (2021)
ISSN:	1422-0067
Popis:	Inflammation is a key underlying factor of age-related macular degeneration (AMD) and inflammasome activation has been linked to disease development. Induced pluripotent stem-cell-derived retinal pigment epithelial cells (iPSC-RPE) are an attractive novel model system that can help to further elucidate disease pathways of this complex disease. Here, we analyzed the effect of dysfunctional protein clearance on inflammation and inflammasome activation in iPSC-RPE cells generated from a patient suffering from age-related macular degeneration (AMD) and an age-matched control. We primed iPSC-RPE cells with IL-1α and then inhibited both proteasomal degradation and autophagic clearance using MG-132 and bafilomycin A1, respectively, causing inflammasome activation. Subsequently, we determined cell viability, analyzed the expression levels of inflammasome-related genes using a PCR array, and measured the levels of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and MCP-1 secreted into the medium. Cell treatments modified the expression of 48 inflammasome-related genes and increased the secretion of mature IL-1β, while reducing the levels of IL-6 and MCP-1. Interestingly, iPSC-RPE from an AMD donor secreted more IL-1β and expressed more Hsp90 prior to the inhibition of protein clearance, while MCP-1 and IL-6 were reduced at both protein and mRNA levels. Overall, our results suggest that cellular clearance mechanisms might already be dysfunctional, and the inflammasome activated, in cells with a disease origin. publishedVersion
Databáze:	OpenAIRE
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