September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Effect of geldanamycin on the NLRP3 inflammasome in human retinal pigment epithelial cells
Author Affiliations & Notes
  • Anu Kauppinen
    School of Pharmacy, University of Eastern Finland, Kuopio, Finland
    Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland
  • Niina Piippo
    School of Pharmacy, University of Eastern Finland, Kuopio, Finland
    Department of Ophthalmology, University of Eastern Finland, Kuopio, Finland
  • Eveliina Korhonen
    School of Pharmacy, University of Eastern Finland, Kuopio, Finland
    Department of Ophthalmology, University of Eastern Finland, Kuopio, Finland
  • Maria Hytti
    School of Pharmacy, University of Eastern Finland, Kuopio, Finland
    Department of Ophthalmology, University of Eastern Finland, Kuopio, Finland
  • Kinnunen Kati
    Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland
  • Kai Kaarniranta
    Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland
    Department of Ophthalmology, University of Eastern Finland, Kuopio, Finland
  • Footnotes
    Commercial Relationships   Anu Kauppinen, None; Niina Piippo, None; Eveliina Korhonen, None; Maria Hytti, None; Kinnunen Kati, None; Kai Kaarniranta, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 485. doi:
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      Anu Kauppinen, Niina Piippo, Eveliina Korhonen, Maria Hytti, Kinnunen Kati, Kai Kaarniranta; Effect of geldanamycin on the NLRP3 inflammasome in human retinal pigment epithelial cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):485.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Age-related macular degeneration (AMD) needs new therapy options. Inflammation plays a major role in AMD, and the prevention of inflammasome signaling serves a possibility to regulate that. Here, we have explored the ability of Hsp90 inhibitor geldanamycin to block the NLRP3 inflammasome in human retinal pigment epithelial (RPE) cells.

Methods : Inflammasome activation was induced in ARPE-19 cells using our existing protocol with MG-132 and bafilomycin A. The effect of Hsp90 inhibition was studied by adding geldanamycin before or after the treatments. Activation of caspase-1 was detected by a commercial assay, and the release of mature IL-1β was measured using the enzyme-linked immunosorbent assay (ELISA) method. Moreover, localization of NLRP3 was determined with western blot and ELISA techniques. Untreated cells as well as those lacking of geldanamycin exposure served as controls. Pairwise analyses for statistical significances were conducted using the Mann-Whitney U test.

Results : Decreased caspase-1 activity (p<0.05) and reduced IL-1β release (p<0.001) showed that geldanamycin is capable of preventing the NLRP3 inflammasome activation in RPE cells. The effect was strongest when geldanamycin was added prior to MG-132. Inflammasome activation decreased the intracellular (p<0.01) and increased the extracellular (p<0.001) levels of NLRP3, and geldanamycin counteracted those effects.

Conclusions : Geldanamycin inhibits the activation of NLRP3 inflammasome in human RPE cells. It most probably affects the initiation step of the process. Therefore, Hsp90 is a potential target in the regulation of inflammasome signaling and thereby in the controlling of AMD pathogenesis.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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