Oxidative stress activates NLRP3 inflammasomes in ARPE-19 cells—Implications for age-related macular degeneration (AMD)
2012; Elsevier BV; Volume: 147; Issue: 1-2 Linguagem: Inglês
10.1016/j.imlet.2012.05.005
ISSN1879-0542
AutoresAnu Kauppinen, Henri Niskanen, Tiina Suuronen, Kati Kinnunen, Antero Salminen, Kai Kaarniranta,
Tópico(s)Heme Oxygenase-1 and Carbon Monoxide
ResumoOxidative 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-1β. The productions of IL-1β 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.
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