Oxidative stress activates NLRP3 inflammasomes in ARPE-19 cells--implications for age-related macular degeneration (AMD).
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-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.
Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland. anu.kauppinen@uef.fi
Anu
A
Kauppinen
Henri
H
Niskanen
Tiina
T
Suuronen
Kati
K
Kinnunen
Antero
A
Salminen
Kai
K
Kaarniranta
D000447:Aldehydes / Q000276:immunology / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008268:Macular Degeneration / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress; D015398:Signal Transduction / Q000187:drug effects
D000447:Aldehydes; D002352:Carrier Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C027576:4-hydroxy-2-nonenal