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NLRP3 Inflammasome Activation in Retinal Pigment Epithelial Cells by Lysosomal Destabilization: Implications for Age-Related Macular Degeneration
Open accessAbstract
PURPOSE: To evaluate the effect of lysosomal destabilization on NLRP3 inflammasome activation in RPE cells and to investigate the mechanisms by which inflammasome activation may contribute to the pathogenesis of age-related macular degeneration (AMD). METHODS: Human ocular tissue sections from patients with geographic atrophy or neovascular AMD were stained for NLRP3 and compared to tissues from age-matched controls. Expression of the IL-1β precursor, pro-IL-1β, was induced in ARPE-19 cells by IL-1α treatment. Immunoblotting was performed to assess expression of NLRP3 inflammasome components (NLRP3, ASC, and procaspase-1) and pro-IL-1β in ARPE-19 cells. Lysosomes were destabilized using the lysosomotropic agent L-leucyl-L-leucine methyl ester (Leu-Leu-OMe). Active caspase-1 was detected using FAM-YVAD-FMK, a fluorescent-labeled inhibitor of caspases (FLICA) specific for caspase-1. IL-1β was detected by immunoblotting and ELISA, and cytotoxicity was evaluated by LDH quantification. RESULTS: RPE of eyes affected by geographic atrophy or neovascular AMD exhibited NLRP3 staining at lesion sites. ARPE-19 cells were found to express NLRP3, ASC, and procaspase-1. IL-1α dose-dependently induced pro-IL-1β expression in ARPE-19 cells. Lysosomal destabilization induced by Leu-Leu-OMe triggered caspase-1 activation, IL-1β secretion, and ARPE-19 cell death. Blocking Leu-Leu-OMe-induced lysosomal disruption with the compound Gly-Phe-CHN(2) or inhibiting caspase-1 with Z-YVAD-FMK abrogated IL-1β release and ARPE-19 cytotoxicity. CONCLUSIONS: NLRP3 upregulation occurs in the RPE during the pathogenesis of advanced AMD, in both geographic atrophy and neovascular AMD. Destabilization of RPE lysosomes induces NLRP3 inflammasome activation, which may contribute to AMD pathology through the release of the proinflammatory cytokine IL-1β and through caspase-1-mediated cell death, known as "pyroptosis."
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Citations
Cites
Origin and physiological roles of inflammation
Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618
Global data on visual impairment in the year 2002.
(2004) · Europe PMC (PubMed Central) · Cited by 4,157
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Duewell, P., Kono, H., Rayner, K. J., Sirois, C. M., Vladimer, G., Bauernfeind, F. G., Abela, G. S., Franchi, L., Nuñez, G., Schnurr, M., et al. (2010) · Nature · doi:10.1038/nature08938 · Cited by 4,026
Pyroptosis: host cell death and inflammation
Bergsbaken, T., Fink, S. L., & Cookson, B. T. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2070 · Cited by 3,183
Hornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., Fitzgerald, K. A., & Latz, E. (2008) · Nature Immunology · doi:10.1038/ni.1631 · Cited by 3,065
Bauernfeind, F. G., Horvath, G., Stutz, A., Alnemri, E. S., MacDonald, K., Speert, D., Fernandes-Alnemri, T., Wu, J., Monks, B. G., Fitzgerald, K. A., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901363 · Cited by 2,959
The NALP3 inflammasome is involved in the innate immune response to amyloid-β
Halle, A., Hornung, V., Petzold, G. C., Stewart, C. R., Monks, B. G., Reinheckel, T., Fitzgerald, K. A., Latz, E., Moore, K. J., & Golenbock, D. T. (2008) · Nature Immunology · doi:10.1038/ni.1636 · Cited by 2,441
Hageman, G. S., Anderson, D. H., Johnson, L. V., Hancox, L. S., Taiber, A. J., Hardisty, L. I., Hageman, J. L., Stockman, H. A., Borchardt, J. D., Gehrs, K. M., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501536102 · Cited by 1,961
AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA
Fernandes-Alnemri, T., Yu, J.-W., Datta, P., Wu, J., & Alnemri, E. S. (2009) · Nature · doi:10.1038/nature07710 · Cited by 1,831
Hageman, G. (2001) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(01)00010-6 · Cited by 1,265
The AMD Genetics Clinical Study Group, Gold, B., Merriam, J. E., Zernant, J., Hancox, L. S., Taiber, A. J., Gehrs, K., Cramer, K., Neel, J., Bergeron, J., et al. (2006) · Nature Genetics · doi:10.1038/ng1750 · Cited by 1,075
Rajamäki, K., Lappalainen, J., Öörni, K., Välimäki, E., Matikainen, S., Kovanen, P. T., & Eklund, K. K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011765 · Cited by 1,039
Current concepts in the pathogenesis of age-related macular degeneration
Zarbin, M. A. (2004) · Archives of Ophthalmology · doi:10.1001/archopht.122.4.598 · Cited by 1,006
Zaki, M. H., Boyd, K. L., Vogel, P., Kastan, M. B., Lamkanfi, M., & Kanneganti, T.-D. (2010) · Immunity · doi:10.1016/j.immuni.2010.03.003 · Cited by 989
Mullins, R. F., Russell, S. R., Anderson, D. H., & Hageman, G. S. (2000) · The FASEB Journal · doi:10.1096/fasebj.14.7.835 · Cited by 937
Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation
Mariathasan, S., & Monack, D. M. (2007) · Nature Reviews Immunology · doi:10.1038/nri1997 · Cited by 869
Oxidative damage-induced inflammation initiates age-related macular degeneration
Hollyfield, J. G., Bonilha, V. L., Rayborn, M. E., Yang, X., Shadrach, K. G., Lu, L., Ufret, R. L., Salomon, R. G., & Perez, V. L. (2008) · Nature Medicine · doi:10.1038/nm1709 · Cited by 710
Para-Inflammation in the Aging Retina
Xu, H., Chen, M., & Forrester, J. V. (2009) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.06.001 · Cited by 659
Drusen complement components C3a and C5a promote choroidal neovascularization
Nozaki, M., Raisler, B. J., Sakurai, E., Sarma, J. V., Barnum, S. R., Lambris, J. D., Chen, Y., Zhang, K., Ambati, B. K., Baffi, J. Z., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408835103 · Cited by 650
RPE lipofuscin and its role in retinal pathobiology
Sparrow, J. R., & Boulton, M. (2005) · Experimental Eye Research · doi:10.1016/j.exer.2005.01.007 · Cited by 644
DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88
Tarallo, V., Hirano, Y., Gelfand, B. D., Dridi, S., Kerur, N., Kim, Y., Cho, W. G., Kaneko, H., Fowler, B. J., Bogdanovich, S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.036 · Cited by 592
Hiscott, J., Marois, J., Garoufalis, J., D'Addario, M., Roulston, A., Kwan, I., Pepin, N., Lacoste, J., Nguyen, H., & Bensi, G. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.10.6231 · Cited by 585
The Inflammasome Mediates UVB-Induced Activation and Secretion of Interleukin-1β by Keratinocytes
Feldmeyer, L., Keller, M., Niklaus, G., Hohl, D., Werner, S., & Beer, H.-D. (2007) · Current Biology · doi:10.1016/j.cub.2007.05.074 · Cited by 544
Suzuki, T., Franchi, L., Toma, C., Ashida, H., Ogawa, M., Yoshikawa, Y., Mimuro, H., Inohara, N., Sasakawa, C., & Nuñez, G. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030111 · Cited by 535
Kummer, J. A., Broekhuizen, R., Everett, H., Agostini, L., Kuijk, L., Martinon, F., Bruggen, R. V., & Tschopp, J. (2007) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.6a7101.2006 · Cited by 531 · cited 1×
“2B).(31) We further confirmed the identity of this band as NLRP3 using a lysate of HEK293T cells overexpressing NLRP3 tagged with DDK (identical to FLAG).”
MethodChen, W., Stambolian, D., Edwards, A. O., Branham, K. E., Othman, M., Jakobsdottir, J., Tosakulwong, N., Pericak-Vance, M. A., Campochiaro, P. A., Klein, M. L., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912702107 · Cited by 506
The Role of Inflammation in the Pathogenesis of Age-related Macular Degeneration
Donoso, L. A., Kim, D., Frost, A., Callahan, A., & Hageman, G. (2006) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2005.12.001 · Cited by 483
Central roles of NLRs and inflammasomes in viral infection
Kanneganti, T.-D. (2010) · Nature Reviews Immunology · doi:10.1038/nri2851 · Cited by 423
Doyle, S. L., Campbell, M., Ozaki, E., Salomon, R. G., Mori, A., Kenna, P. F., Farrar, G. J., Kiang, A.-S., Humphries, M. M., Lavelle, E. C., et al. (2012) · Nature Medicine · doi:10.1038/nm.2717 · Cited by 422
Activation of the IL-1β-Processing Inflammasome Is Involved in Contact Hypersensitivity
Watanabe, H., Gaide, O., Pétrilli, V., Martinon, F., Contassot, E., Roques, S., Kummer, J. A., Tschopp, J., & French, L. E. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700819 · Cited by 416
The potential angiogenic role of macrophages in the formation of choroidal neovascular membranes.
Oh, H., Takagi, H., Takagi, C., Suzuma, K., Otani, A., Ishida, K., Matsumura, M., Ogura, Y., & Honda, Y. (1999) · PubMed · Cited by 393
Inflammasomes: current understanding and open questions
Bauernfeind, F., Ablasser, A., Bartok, E., Kim, S., Schmid-Burgk, J., Cavlar, T., & Hornung, V. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0567-4 · Cited by 359
Inflammasomes: too big to miss
Stutz, A., Golenbock, D. T., & Latz, E. (2009) · Journal of Clinical Investigation · doi:10.1172/jci40599 · Cited by 346
A2E, a lipofuscin fluorophore, in human retinal pigmented epithelial cells in culture.
Sparrow, J. R., Parish, C. A., Hashimoto, M., & Nakanishi, K. (1999) · PubMed · Cited by 310
Niemi, K., Teirilä, L., Lappalainen, J., Rajamäki, K., Baumann, M. H., Öörni, K., Wolff, H., Kovanen, P. T., Matikainen, S., & Eklund, K. K. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002843 · Cited by 298
Critical functions of priming and lysosomal damage for NLRP3 activation
Hornung, V., & Latz, E. (2010) · European Journal of Immunology · doi:10.1002/eji.200940185 · Cited by 297
Thiele, D. L., & Lipsky, P. E. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.1.83 · Cited by 261
Kumar, M. V., Nagineni, C. N., Chin, M. S., Hooks, J. J., & Detrick, B. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.04.018 · Cited by 243
Heurich, M., Martínez-Barricarte, R., Francis, N. J., Roberts, D. L., Rodríguez de Córdoba, S., Morgan, B. P., & Harris, C. L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019338108 · Cited by 231
Age related macular degeneration and drusen: Neuroinflammation in the retina
Buschini, E., Piras, A., Nuzzi, R., & Vercelli, A. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.05.011 · Cited by 230
Kinnunen, K., Petrovski, G., Moe, M. C., Berta, A., & Kaarniranta, K. (2012) · Acta Ophthalmologica · doi:10.1111/j.1755-3768.2011.02179.x · Cited by 197
Self-citationExpression and Role of VEGF in the Adult Retinal Pigment Epithelium
Ford, K. M., Saint-Geniez, M., Walshe, T., Zahr, A., & D'Amore, P. A. (2011) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.11-8353 · Cited by 180
Self-citationSoluble and Mature Amyloid Fibrils in Drusen Deposits
Isas, J. M., Luibl, V., Johnson, L. V., Kayed, R., Wetzel, R. B., Glabe, C. G., Langen, R., & Chen, J. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.09-4207 · Cited by 159
Yilmaz, Ö., Sater, A. A. A., Yao, L., Koutouzis, T., Pettengill, M. A., & Ojcius, D. M. (2009) · Cellular Microbiology · doi:10.1111/j.1462-5822.2009.01390.x · Cited by 150
Disease-associated amyloid and misfolded protein aggregates activate the inflammasome
Masters, S. L., & O'Neill, L. A. J. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.01.005 · Cited by 135
Promotion of adhesion and migration of RPE cells to provisional extracellular matrices by TNF-alpha.
Jin, M., He, S., Woerpel, V., Ryan, S. J., & Hinton, D. R. (2000) · PubMed · Cited by 104
Gnana‐Prakasam, J. P., Martin, P. M., Mysona, B. A., Roon, P., Smith, S. B., & Ganapathy, V. (2008) · Biochemical Journal · doi:10.1042/bj20071377 · Cited by 95
Schütt, F., Bergmann, M., Holz, F. G., & Kopitz, J. (2002) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-002-0558-8 · Cited by 90
Kindzelskii, A. L., Elner, V. M., Elner, S. G., Yang, D., Hughes, B. A., & Petty, H. R. (2004) · The Journal of General Physiology · doi:10.1085/jgp.200409062 · Cited by 86
Kaarniranta, K., & Salminen, A. (2008) · Journal of Molecular Medicine · doi:10.1007/s00109-008-0418-z · Cited by 77
Lichtlen, P., Lam, T. T., Nork, T. M., Streit, T., & Urech, D. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.09-4890 · Cited by 76
C.WANG, X., Jobin, C., Allen, J. B., Roberts, W. L., & Jaffe, G. J. (1999) · PubMed · Cited by 66
Planck, S. R., Huang, X.-N., Robertson, J. E., et al. (1993) · Current Eye Research · doi:10.3109/02713689308999465 · Cited by 61
Sandwich ELISA formats designed to detect 17 kDa IL-1β significantly underestimate 35 kDa IL-1β
Herzyk, D. J., Berger, A. E., Allen, J. N., & Wewers, M. D. (1992) · Journal of Immunological Methods · doi:10.1016/0022-1759(92)90178-v · Cited by 57
Ravanko, K., Järvinen, K., Helin, J., Kalkkinen, N., & Hölttä, E. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2993 · Cited by 47
Jasielska, M., Semkova, I., Shi, X., Schmidt, K., Karagiannis, D. A., Kokkinou, D., Mackiewicz, J., Kociok, N., & Joussen, A. M. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.09-5003 · Cited by 46
Human RPE Expression of Cell Survival Factors
Yang, P., Wiser, J. L., Peairs, J. J., Ebright, J. N., Zavodni, Z. J., Rickman, C. B., & Jaffe, G. J. (2005) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.04-1039 · Cited by 40
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NLRP3 inflammasome and its inhibitors: a review
Shao, B.-Z., Xu, Z.-Q., Han, B.-Z., Su, D.-F., & Liu, C. (2015) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00262 · Cited by 836
“…Ca2+ overload (Iyer et al., 2013; Miao et al., 2014; Zhuang et al., 2015), lysosomal disruption (Hornung et al., 2008; Sheedy et al., 2013; Tseng et al., 2013), autophagic dysfunction (Cho et al., 2014; Shao et al., 2014; Jabir et al., 2015) and the activity of thioredoxin-interacting…”
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Datta, S., Cano, M., Ebrahimi, K., Wang, L., & Handa, J. T. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.03.002 · Cited by 802
Inflammation and its role in age-related macular degeneration
Kauppinen, A., Paterno, J. J., Blasiak, J., Salminen, A., & Kaarniranta, K. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2147-8 · Cited by 649
Immunology of age-related macular degeneration
Ambati, J., Atkinson, J. P., & Gelfand, B. D. (2013) · Nature Reviews Immunology · doi:10.1038/nri3459 · Cited by 584
T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4 + T cells
Arbore, G., West, E. E., Spolski, R., Robertson, A. A. B., Klos, A., Rheinheimer, C., Dutow, P., Woodruff, T. M., Yu, Z. X., O’Neill, L. A., et al. (2016) · Science · doi:10.1126/science.aad1210 · Cited by 513
Metadata
- Authors
- Tseng, W. A., Thein, T., Kinnunen, K., Lashkari, K., Gregory, M. S., D'Amore, P. A., & Ksander, B. R.
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2013-01-07
- Volume
- 54
- Issue
- 1
- Pages
- 110
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- OpenAlex
- W2059563381
- Cited by
- 290
- References
- 57
- FWCI
- 7.20
- Type
- journal article
- Language
- en
- Open access
- bronze
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