Oxidative stress activates NLRP3 inflammasomes in ARPE-19 cells¡ªImplications for age-related macular degeneration (AMD)

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• 作者：Anu Kauppinen ; Henri Niskanen ; Tiina Suuronen ; Kati Kinnunen ; Antero Salminen ; Kai Kaarniranta
• 关键词：Age-related macular degeneration (AMD) ; Aging ; Inflammasome ; Inflammation ; NLRP3 ; Retinal pigment epithelium (RPE)
• 刊名：Immunology Letters
• 出版年：2012
• 出版时间：September-October, 2012
• 年：2012
• 卷：147
• 期：1-2
• 页码：29-33
• 全文大小：453 K

文摘

Oxidative stress and inflammation are known to be associated with age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells play the principal role in the immune defense of macula, and their dysfunction is a crucial event leading to clinically relevant changes seen in AMD. In the present study, we have examined the ability of oxidative stress to activate inflammasome signaling in the human ARPE-19 cells by adding the lipid peroxidation end product 4-hydroxynonenal (HNE) to cell cultures pre-treated or not treated with the endotoxin, LPS. Our results indicate that LPS and HNE significantly increased the production of IL-6 and IL-18, respectively. LPS treatment preceding HNE induced an even greater increase in the production of IL-18 than HNE alone. In addition to IL-18, HNE significantly increased the production of IL-1¦Â. The productions of IL-1¦Â and IL-18 were reduced in the cell cultures pre-treated with the Caspase-1 inhibitor. PCR analysis revealed that HNE induced an over 5-fold increase in the amount of NLRP3 mRNA compared to control cells; LPS had no effect. In conclusion, our present data suggest that oxidative stress can activate NLRP3 inflammasomes in RPE cells which occupy center stage in the pathogenesis of AMD.