DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88
Open accessAbstract
Alu RNA accumulation due to DICER1 deficiency in the retinal pigmented epithelium (RPE) is implicated in geographic atrophy (GA), an advanced form of age-related macular degeneration that causes blindness in millions of individuals. The mechanism of Alu RNA-induced cytotoxicity is unknown. Here we show that DICER1 deficit or Alu RNA exposure activates the NLRP3 inflammasome and triggers TLR-independent MyD88 signaling via IL18 in the RPE. Genetic or pharmacological inhibition of inflammasome components (NLRP3, Pycard, Caspase-1), MyD88, or IL18 prevents RPE degeneration induced by DICER1 loss or Alu RNA exposure. These findings, coupled with our observation that human GA RPE contains elevated amounts of NLRP3, PYCARD, and IL18 and evidence of increased Caspase-1 and MyD88 activation, provide a rationale for targeting this pathway in GA. Our findings also reveal a function of the inflammasome outside the immune system and an immunomodulatory action of mobile elements.
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AMD has been associated with downregulation of DICER1, and consequent elevation of Alu RNA levels activates the NLRP3 inflammasome in retinal pigmented epithelial cells, leading to cytotoxicity and degeneration.
“AMD has been associated with the downregulation DICER1, and the consequent elevation of Alu RNA levels activates the NLRP3 (NOD, LRR and pyrin domain containing protein 3) inflammasome in retinal pigmented epithelial cells, leading to cytotoxicity and degeneration128.”
From The role of retrotransposable elements in ageing and age-associated diseases (2021) · cites this paper as [128]
Alu RNA activates the NLRP3 inflammasome, stimulating cytokine production and MyD88-induced cytotoxicity of RPE cells, thus contributing to the etiology of GA.
“The latter then activates the NLRP3 inflammasome, stimulating cytokine production and MyD88-induced cytotoxicity of RPE cells, thus contributing to the etiology of GA (Tarallo et al., 2012).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Tarallo et al., 2012
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Initial sequencing and analysis of the human genome
International Human Genome Sequencing Consortium, Whitehead Institute for Biomedical Research, C. F. G. R., Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., Devon, K., Dewar, K., et al. (2001) · Nature · doi:10.1038/35057062 · Cited by 24,216 · see citing works
Pathogen Recognition and Innate Immunity
Akira, S., Uematsu, S., & Takeuchi, O. (2006) · Cell · doi:10.1016/j.cell.2006.02.015 · Cited by 11,974 · see citing works
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207 · see citing works
Self-citationRecognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001) · Nature · doi:10.1038/35099560 · Cited by 6,129 · see citing works
A role for mitochondria in nlrp3 inflammasome activation
Zhou, R., Yazdi, A. S., Menu, P., & Tschopp, J. (2011) · Nature · doi:10.1038/nature09663 · Cited by 5,602 · see citing works
Schroder, K., & Tschopp, J. (2010) · Cell · doi:10.1016/j.cell.2010.01.040 · Cited by 5,475 · see citing works
Role for a bidentate ribonuclease in the initiation step of RNA interference
Bernstein, E., Caudy, A. A., Hammond, S. M., & Hannon, G. J. (2001) · Nature · doi:10.1038/35053110 · Cited by 4,896 · see citing works
Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8
Heil, F., Hemmi, H., Hochrein, H., Ampenberger, F., Kirschning, C., Akira, S., Lipford, G., Wagner, H., & Bauer, S. (2004) · Science · doi:10.1126/science.1093620 · Cited by 3,947 · see citing works
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K. J., et al. (2006) · Nature · doi:10.1038/nature04734 · Cited by 3,888 · see citing works
Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA
Diebold, S. S., Kaisho, T., Hemmi, H., Akira, S., & Reis e Sousa, C. (2004) · Science · doi:10.1126/science.1093616 · Cited by 3,444 · see citing works
Role of Adaptor TRIF in the MyD88-Independent Toll-Like Receptor Signaling Pathway
Yamamoto, M., Sato, S., Hemmi, H., Hoshino, K., Kaisho, T., Sanjo, H., Takeuchi, O., Sugiyama, M., Okabe, M., Takeda, K., et al. (2003) · Science · doi:10.1126/science.1087262 · Cited by 3,244 · see citing works
Cryopyrin activates the inflammasome in response to toxins and ATP
Mariathasan, S., Weiss, D. S., Newton, K., McBride, J., O'Rourke, K., Roose-Girma, M., Lee, W. P., Weinrauch, Y., Monack, D. M., & Dixit, V. M. (2006) · Nature · doi:10.1038/nature04515 · Cited by 3,080 · see citing works
Nakahira, K., Haspel, J. A., Rathinam, V. A. K., Lee, S.-J., Dolinay, T., Lam, H. C., Englert, J. A., Rabinovitch, M., Cernadas, M., Kim, H. P., et al. (2011) · Nature Immunology · doi:10.1038/ni.1980 · Cited by 3,049 · see citing works
A novel heterodimeric cysteine protease is required for interleukin-1βprocessing in monocytes
Thornberry, N., Bull, H., Calaycay, J., Chapman, K., Howard, A., Kostura, M., Miller, D. K., Molineaux, S., Weidner, J., Auniņš, J., et al. (1992) · Nature · doi:10.1038/356768a0 · Cited by 2,725 · see citing works
The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling
O'Neill, L. A. J., & Bowie, A. G. (2007) · Nature Reviews Immunology · doi:10.1038/nri2079 · Cited by 2,667 · see citing works
5'-Triphosphate RNA Is the Ligand for RIG-I
Hornung, V., Ellegast, J., Kim, S., Brzózka, K., Jung, A., Kato, H., Poeck, H., Akira, S., Conzelmann, K.-K., Schlee, M., et al. (2006) · Science · doi:10.1126/science.1132505 · Cited by 2,474 · see citing works
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 · see citing works
The Inflammasomes: Guardians of the Body
Martinon, F., Mayor, A., & Tschopp, J. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132715 · Cited by 2,436 · see citing works
Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function.
Adachi, O., Kawai, T., Takeda, K., Matsumoto, M., Tsutsui, H., Sakagami, M., Nakanishi, K., & Akira, S. (1998) · Immunity · doi:10.1016/s1074-7613(00)80596-8 · Cited by 2,358 · see citing works
NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production?
Tschopp, J., & Schroder, K. (2010) · Nature reviews. Immunology · doi:10.1038/nri2725 · Cited by 1,859 · see citing works
Fatty acid–induced NLRP3-ASC inflammasome activation interferes with insulin signaling
Wen, H., Gris, D., Lei, Y. L., Jha, S., Zhang, L., Huang, M. T.-H., Brickey, W. J., & Ting, J. P. ‐. (2011) · Nature Immunology · doi:10.1038/ni.2022 · Cited by 1,811 · see citing works
Alu repeats and human genomic diversity
Batzer, M., & Deininger, P. (2002) · Nature reviews genetics · doi:10.1038/nrg798 · Cited by 1,522 · see citing works
Oncogenically active MYD88 mutations in human lymphoma
Ngo, V. N., Young, R. M., Schmitz, R., Jhavar, S. G., Xiao, W., Lim, K., Kohlhammer, H., Xu, W., Yang, Y., Zhao, H., et al. (2010) · Nature · doi:10.1038/nature09671 · Cited by 1,514 · see citing works
Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
Puente, X. S., Pinyol, M., Quesada, V., Conde, L., Ordóñez, G. R., Villamor, N., Escaramís, G., Jares, P., Beà, S., González, M., et al. (2011) · Nature · doi:10.1038/nature10113 · Cited by 1,512 · see citing works
Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria
Miao, E. A., Leaf, I. A., Treuting, P. M., Mao, D. P., Dors, M., Sarkar, A., Warren, S. E., Wewers, M. D., & Aderem, A. (2010) · Nature Immunology · doi:10.1038/ni.1960 · Cited by 1,336 · see citing works
Masters, S. L., Dunne, A., Subramanian, S. L., Hull, R. L., Tannahill, G. M., Sharp, F. A., Becker, C., Franchi, L., Yoshihara, E., Chen, Z., et al. (2010) · Nature Immunology · doi:10.1038/ni.1935 · Cited by 1,330 · cited 1× · see citing works
“Subsequently, endogenous crystals, polypeptides, and lipids were reported to activate it in diseases such as gout, atherogenesis, Alzheimer’s disease, and type 2 diabetes (Halle et al., 2008; Masters et al., 2010; Muruve et al., 2008; Wen et al., 2011).”
Pyogenic Bacterial Infections in Humans with MyD88 Deficiency
von Bernuth, H., Pïcard, C., Jin, Z., Sranujit, R. P., Xiao, H. Q., Ku, C., Chrabieh, M., Ben‐Mustapha, I., Ghandil, P., Çamcıoğlu, Y., et al. (2008) · Science · doi:10.1126/science.1158298 · Cited by 1,287 · see citing works
Identification of Lps2 as a key transducer of MyD88-independent TIR signalling
Hoebe, K. H. N., Du, X., Georgel, P., Janssen, E. M., Tabeta, K., Kim, S. O., Goode, J., Lin, P., Mann, N., Mudd, S., et al. (2003) · Nature · doi:10.1038/nature01889 · Cited by 1,232 · see citing works
Caspase-1 processes IFN-γ-inducing factor and regulates LPS-induced IFN- γ production
Ghayur, T., Banerjee, S., Hugunin, M., Butler, D., Herzog, L., Carter, A. B., Quintal, L. J., Sekut, L., Talanian, R. V., Paskind, M. P., et al. (1997) · Nature · doi:10.1038/386619a0 · Cited by 1,204 · see citing works
Targeting Antioxidants to Mitochondria by Conjugation to Lipophilic Cations
Murphy, M. P., & Smith, R. A. J. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105110 · Cited by 1,173 · see citing works
Self-citationIRAK (Pelle) Family Member IRAK-2 and MyD88 as Proximal Mediators of IL-1 Signaling
Muzio, M., Ni, J., Feng, P., & Dixit, V. M. (1997) · Science · doi:10.1126/science.278.5343.1612 · Cited by 1,170 · see citing works
Activation of Interferon-γ Inducing Factor Mediated by Interleukin-1β Converting Enzyme
Gu, Y., Kuida, K., Tsutsui, H., Ku, G., Hsiao, K., Fleming, M. A., Hayashi, N., Higashino, K., Okamura, H., Nakanishi, K., et al. (1997) · Science · doi:10.1126/science.275.5297.206 · Cited by 1,159 · see citing works
Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3
Kanneganti, T., Özören, N., Body–Malapel, M., Amer, A. O., Park, J., Franchi, L., Whitfield, J. R., Barchet, W., Colonna, M., Vandenabeele, P., et al. (2006) · Nature · doi:10.1038/nature04517 · Cited by 1,149 · see citing works
Self-citationThe NLRP3 Inflammasome: A Sensor for Metabolic Danger?
Schroder, K., Zhou, R., & Tschopp, J. (2010) · Science · doi:10.1126/science.1184003 · Cited by 1,131 · see citing works
Fink, S. L., & Cookson, B. T. (2006) · Cellular Microbiology · doi:10.1111/j.1462-5822.2006.00751.x · Cited by 1,114 · see citing works
Risk factors for age-related macular degeneration
Smith, W., Assink, J., Klein, R., Mitchell, P., Klaver, C. C. W., Klein, B. E. K., Hofman, A., Jensen, S., Wang, J. J., & de Jong, P. T. V. M. (2001) · Ophthalmology · doi:10.1016/s0161-6420(00)00580-7 · Cited by 1,071 · see citing works
Fernandes-Alnemri, T., Wu, J., Yu, J.-W., Datta, P., Miller, B., Jankowski, W., Rosenberg, S., Zhang, J., & Alnemri, E. S. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402194 · Cited by 1,026 · see citing works
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 · see citing works
Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies
Ambati, J., Ambati, B. K., Yoo, S. H., Ianchulev, S., & Adamis, A. P. (2003) · Survey of Ophthalmology · doi:10.1016/s0039-6257(03)00030-4 · Cited by 959 · see citing works
Self-citationThe inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response
Muruve, D. A., Pétrilli, V., Zaiss, A. K., White, L. R., Clark, S. A., Ross, P. J., Parks, R. J., & Tschopp, J. (2008) · Nature · doi:10.1038/nature06664 · Cited by 936 · see citing works
Sequence- and target-independent angiogenesis suppression by siRNA via TLR3
Kleinman, M. E., Yamada, K., Takeda, A., Chandrasekaran, V., Nozaki, M., Baffi, J., Albuquerque, R., Yamasaki, S., Itaya, M., Pan, Y., et al. (2008) · Nature · doi:10.1038/nature06765 · Cited by 931 · see citing works
Self-citationType I Interferon Inhibits Interleukin-1 Production and Inflammasome Activation
Guarda, G., Braun, M., Staehli, F., Tardivel, A., Mattmann, C., Förster, I., Farlik, M., Decker, T., Pasquier, R. D., Romero, P. J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.02.006 · Cited by 924 · see citing works
IRAK: A Kinase Associated with the Interleukin-1 Receptor
Cao, Z., Henzel, W. J., & Gao, X. (1996) · Science · doi:10.1126/science.271.5252.1128 · Cited by 898 · see citing works
Savina, A., Jancic, C. C., Hugues, S., Guermonprez, P., Vargas, P., Moura, I. C., Lennon‐Duménil, A., Seabra, M. C., Raposo, G., & Amigorena, S. (2006) · Cell · doi:10.1016/j.cell.2006.05.035 · Cited by 896 · see citing works
Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4
Suzuki, N., Suzuki, S., Duncan, G. S., Millar, D. G., Wada, T., Mirtsos, C., Takada, H., Wakeham, A. C., Itié, A., Li, S., et al. (2002) · Nature · doi:10.1038/nature736 · Cited by 858 · see citing works
Active Caspase-1 Is a Regulator of Unconventional Protein Secretion
Keller, M., Rüegg, A., Werner, S., & Beer, H. (2008) · Cell · doi:10.1016/j.cell.2007.12.040 · Cited by 851 · see citing works
Ocular immune privilege: therapeutic opportunities from an experiment of nature
Streilein, J. W. (2003) · Nature Reviews Immunology · doi:10.1038/nri1224 · Cited by 807 · see citing works
Tabeta, K., Hoebe, K. H. N., Janssen, E. M., Du, X., Georgel, P., Crozat, K., Mudd, S., Mann, N., Sovath, S., Goode, J., et al. (2006) · Nature Immunology · doi:10.1038/ni1297 · Cited by 736 · see citing works
NALPs: a novel protein family involved in inflammation
Tschopp, J., Martinon, F., & Burns, K. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1019 · Cited by 719 · see citing works
Deficient signaling in mice devoid of double‐stranded RNA‐dependent protein kinase.
Yang, Y. L., Reis, L. F. L., Pavlovic, J., Aguzzi, A., Schäfer, R., Kumar, A., Williams, B. R. G., Aguet, M., & Weissmann, C. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00300.x · Cited by 632 · see citing works
Bauernfeind, F., Bartok, E., Rieger, A., Franchi, L., Núñez, G., & Hornung, V. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100613 · Cited by 617 · see citing works
Self-citationRey, F. E., Cifuentes-Pagano, E., Kiarash, A., Quinn, M. T., & Pagano, P. J. (2001) · Circulation Research · doi:10.1161/hh1701.096037 · Cited by 606 · see citing works
The Specific and Essential Role of MAVS in Antiviral Innate Immune Responses
Sun, Q., Sun, L., Liu, H.-H., Chen, X., Seth, R. B., Forman, J., & Chen, Z. J. (2006) · Immunity · doi:10.1016/j.immuni.2006.04.004 · Cited by 604 · see citing works
DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration
Kaneko, H., Dridi, S., Tarallo, V., Gelfand, B. D., Fowler, B. J., Cho, W. G., Kleinman, M. E., Ponicsan, S. L., Hauswirth, W. W., Chiodo, V. A., et al. (2011) · Nature · doi:10.1038/nature09830 · Cited by 601 · see citing works
Self-citationLopez, P. F., Sippy, B., Lambert, H. M., Thach, A. B., & Hinton, D. R. (1998) · Retina · doi:10.1097/00006982-199805000-00035 · Cited by 592 · see citing works
Self-citationRelationship between RPE and Choriocapillaris in Age-Related Macular Degeneration
McLeod, D. S., Grebe, R. R., Bhutto, I. A., Merges, C. A., Baba, T., & Lutty, G. A. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.09-3639 · Cited by 568 · see citing works
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 · see citing works
Blaauwgeers, H. G. T., Holtkamp, G. M., Rutten, H., Witmer, A. N., Koolwijk, P., Partanen, T. A., Alitalo, K. K., Kroon, M. E., Kijlstra, A., van Hinsbergh, V. W. M., et al. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65138-3 · Cited by 520 · see citing works
Essential role of IPS-1 in innate immune responses against RNA viruses
Kumar, H., Kawai, T., Kato, H., Sato, S., Takahashi, K., Coban, C., Yamamoto, M., Uematsu, S., Ishii, K. J., Takeuchi, O., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060792 · Cited by 503 · see citing works
IFIT1 is an antiviral protein that recognizes 5′-triphosphate RNA
Pichlmair, A., Lassnig, C., Eberle, C.-A., Górna, M. W., Baumann, C., Burkard, T. R., Bürckstümmer, T., Stefanovic, A., Krieger, S., Bennett, K. L., et al. (2011) · Nature Immunology · doi:10.1038/ni.2048 · Cited by 485 · see citing works
Li, Y., & Trush, M. A. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9729 · Cited by 479 · see citing works
Clinical Features and Outcome of Patients With IRAK-4 and MyD88 Deficiency
Pïcard, C., von Bernuth, H., Ghandil, P., Chrabieh, M., Levy, O., Arkwright, P. D., McDonald, D. R., Geha, R. S., Takada, H., Krause, J. C., et al. (2010) · Medicine · doi:10.1097/md.0b013e3181fd8ec3 · Cited by 425 · see citing works
Fink, S. L., Bergsbaken, T., & Cookson, B. T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707370105 · Cited by 403 · see citing works
Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration
Feher, J., Kovacs, I., Artico, M., Cavallotti, C., Papale, A., & Balacco Gabrieli, C. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.05.012 · Cited by 388 · see citing works
Crystal structure of a PIWI protein suggests mechanisms for siRNA recognition and slicer activity
Parker, J. S., Roe, S. M., & Barford, D. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600488 · Cited by 350 · see citing works
Lopez, P. F., Sippy, B. D., Lambert, H. M., Thach, A. B., & Hinton, D. R. (1996) · PubMed · Cited by 331 · see citing works
Self-citationActive Alu retrotransposons in the human genomePreprint
Bennett, E. A., Keller, H., Mills, R. E., Schmidt, S., Moran, J. V., Weichenrieder, O., & Devine, S. E. (2008) · Genome Research · doi:10.1101/gr.081737.108 · Cited by 274 · see citing works
Meissner, F., Seger, R. A., Moshous, D., Fischer, A., Reichenbach, J., & Zychlinsky, A. (2010) · Blood · doi:10.1182/blood-2010-01-264218 · Cited by 269 · see citing works
CCR3 is a target for age-related macular degeneration diagnosis and therapy
Takeda, A., Baffi, J. Z., Kleinman, M. E., Cho, W. G., Nozaki, M., Yamada, K., Kaneko, H., Albuquerque, R. J. C., Dridi, S., Saito, K., et al. (2009) · Nature · doi:10.1038/nature08151 · Cited by 263 · see citing works
Self-citationT cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes
Guarda, G., Dostert, C., Staehli, F., Cabalzar, K., Castillo, R., Tardivel, A., Schneider, P., & Tschopp, J. (2009) · Nature · doi:10.1038/nature08100 · Cited by 250 · see citing works
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 · see citing works
Toll-like Receptor 3 and Geographic Atrophy in Age-Related Macular Degeneration
Yang, Z., Stratton, C., Francis, P. J., Kleinman, M. E., Tan, P. L., Gibbs, D., Tong, Z., Chen, H., Constantine, R., Yang, X., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802437 · Cited by 222 · see citing works
Self-citationCaspase Inhibitors Promote Alternative Cell Death Pathways
Vandenabeele, P., Berghe, T. V., & Festjens, N. (2006) · Science s STKE · doi:10.1126/stke.3582006pe44 · Cited by 215 · see citing works
MyD88-mediated stabilization of interferon-γ-induced cytokine and chemokine mRNA
Sun, D., & Ding, A. H. (2006) · Nature Immunology · doi:10.1038/ni1308 · Cited by 206 · see citing works
Human nlrp3 inflammasome activation is nox1-4 independent
van Bruggen, R., Köker, M. Y., Jansen, M., van Houdt, M., Roos, D., Kuijpers, T. W., & van den Berg, T. K. (2010) · Blood · doi:10.1182/blood-2009-10-250803 · Cited by 202 · see citing works
Kanakaraj, P., Ngo, K., Wu, Y., Angulo, A., Ghazal, P., Harris, C. A., Siekierka, J., Peterson, P. A., & Fung-Leung, W. (1999) · Journal of Experimental Medicine · doi:10.1084/jem.189.7.1129 · Cited by 196 · see citing works
Nordgaard, C. L., Karunadharma, P. P., Feng, X., Olsen, T. W., & Ferrington, D. A. (2008) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-1352 · Cited by 188 · see citing works
Loiarro, M., Sette, C., Gallo, G., Ciacci, A., Fantò, N., Mastroianni, D., Carminati, P., & Ruggiero, V. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c400613200 · Cited by 177 · see citing works
Lin, H., Xu, H. C., Liang, F.-Q., Liang, H., Gupta, P. K., Havey, A., Boulton, M. E., & Godley, B. F. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-6163 · Cited by 163 · see citing works
Qureshi, N., Takayama, K., & Kurtz, R. S. (1991) · Infection and Immunity · doi:10.1128/iai.59.1.441-444.1991 · Cited by 135 · see citing works
Verhoef, P. A., Kertesy, S. B., Lundberg, K. C., Kahlenberg, J. M., & Dubyak, G. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.11.7623 · Cited by 124 · see citing works
Alu RNA secondary structure consists of two independent 7 SL RNA-like folding units
Sinnett, D., Richer, C., Deragon, J., et al. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)31497-2 · Cited by 111 · see citing works
Vogt, S. D., Curcio, C. A., Wang, L., Li, C.-M., McGwin, G., Medeiros, N. E., Philp, N. J., Kimble, J. A., & Read, R. W. (2011) · Experimental Eye Research · doi:10.1016/j.exer.2011.06.002 · Cited by 104 · see citing works
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Yang, P., Tyrrell, J., Han, I. C., & Jaffe, G. J. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-3202 · Cited by 77 · see citing works
Dhellin, O., Maestre, J., & Heidmann, T. (1997) · The EMBO Journal · doi:10.1093/emboj/16.21.6590 · Cited by 76 · see citing works
Bogdanovich, S., McNally, E. M., & Khurana, T. S. (2007) · Muscle & Nerve · doi:10.1002/mus.20920 · Cited by 74 · see citing works
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cDNAs derived from primary and small cytoplasmic Alu (scAlu) transcripts
Shaikh, T. H., Roy, A. M., Kim, J., et al. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1161 · Cited by 68 · see citing works
NOX-free inflammasome activation
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Self-citation
- Authors
- Tarallo, V., Hirano, Y., Gelfand, B. D., Dridi, S., Kerur, N., Kim, Y., Cho, W. G., Kaneko, H., Fowler, B. J., Bogdanovich, S., Albuquerque, R. J. C., Hauswirth, W. W., Chiodo, V. A., Kugel, J. F., Goodrich, J. A., Ponicsan, S. L., Chaudhuri, G., Murphy, M. P., Dunaief, J. L., Ambati, B. K., Ogura, Y., Yoo, J. W., Lee, D.-K., Provost, P., Hinton, D. R., Núñez, G., Baffi, J. Z., Kleinman, M. E., & Ambati, J.
- Affiliations
- University of Kentucky (US)
- University of Florida (US)
- University of Colorado Boulder (US)
- Meharry Medical College (US)
- MRC Mitochondrial Biology Unit (GB)
- University of Pennsylvania (US)
- University of Utah (US)
- Nagoya City University (JP)
- Sungkyunkwan University (KR)
- Centre hospitalier universitaire de Québec (CA)
- University of Southern California (US)
- University of Michigan (US)
- Corresponding author
- Ambati, Jayakrishna
- ORCID
- Tarallo, Valeria
- Hirano, Yoshio
- Gelfand, Bradley D.
- Dridi, Sami
- Kerur, Nagaraj
- Cho, Won Gil
- Kaneko, Hiroki
- Fowler, Benjamin J.
- Bogdanovich, Sasha
- Hauswirth, William W.
- Chiodo, Vince A.
- Kugel, Jennifer F.
- Goodrich, James A.
- Murphy, Michael P.
- Dunaief, Joshua L.
- Ambati, Balamurali K.
- Ogura, Yuichiro
- Lee, Dong-ki
- Provost, Patrick
- Hinton, David R.
- Núñez, Gabriel
- Kleinman, Mark E.
- Ambati, Jayakrishna
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 149
- Issue
- 4
- Pages
- 847-859
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3351582
- OpenAlex
- W2111586778
- Cited by
- 592
- References
- 93
- Citations by year
- 2026: 17 · 2025: 19 · 2024: 41 · 2023: 32 · 2022: 39 · 2021: 57 · 2020: 53 · 2019: 34 · 2018: 48 · 2017: 40 · 2016: 46 · 2015: 53 · 2014: 53 · 2013: 38 · 2012: 21
- FWCI
- 21.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (TL1TR000115, 1ul1rr033173-01, UL1TR000117, UL1TR001998)
- National Heart, Lung, and Blood Institute (T32HL091812)
- National Eye Institute (R01EY020672, P30EY003040, R01EY017950, P30EY021721, R01EY018836, K08EY021521, R01EY001545, R01EY018350, R21EY019778, RC1EY020442, R01EY017182, K08EY021757, R01EY022238)
- National Institute of General Medical Sciences (R01GM068414)
- National Institute of Allergy and Infectious Diseases (R01AI063331)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR052756)
- National Center for Research Resources (UL1RR-033173, TL1RR033172)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- DICER1, Alu RNA, age-related macular degeneration, geographic atrophy, retinal pigment epithelium, NLRP3 inflammasome, MyD88 signaling, IL-18, caspase-1, PYCARD, transposable elements, RNA interference, retinal degeneration
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Carrier Proteins, Humans, Alu Elements, Ribonuclease III, Toll-Like Receptors, Mice, DEAD-box RNA Helicases, Myeloid Differentiation Factor 88, Retinal Pigment Epithelium, Geographic Atrophy, Inflammasomes
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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