Abstract
The NLRP3 inflammasome, which consists of the NLRP3 (nucleotide-binding oligomerization domain (Nod)-like receptor 3) scaffold, the ASC (apoptosis-associated speck-like protein containing a CARD) adaptor and procaspase- 1, is assembled after the cytoplasmic LRRs (leucine-rich repeats) of NLRP3 sense pathogens or danger signals. The NLRP3 inflammasome controls the activation of the proteolytic enzyme caspase-1. Caspase-1 in turn regulates the maturation of the proinflammasome cytokines IL-1β and IL-18, which leads to an inflammatory response. The inflammasome plays an important role in the development of Alzheimer’s disease and bacterial meningitis, and the NLRP3 inflammasome may become a new target for the prevention and treatment of central nervous system diseases.
Keywords: NLRP3, inflammasome, central nervous system
References
- [1].Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Goutassociated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440:237–241. doi: 10.1038/nature04516. [DOI] [PubMed] [Google Scholar]
- [2].Schoultz I, Verma D, Halfvarsson J, Torkvist L, Fredrikson M, Sjoqvist U, et al. Combined polymorphisms in genes encoding the inflammasome components NALP3 and CARD8 confer susceptibility to Crohn’s disease in Swedish men. Am J Gastroenterol. 2009;104:1180–1188. doi: 10.1038/ajg.2009.29. [DOI] [PubMed] [Google Scholar]
- [3].Roberts RL, Topless RK, Phipps-Green AJ, Gearry RB, Barclay ML, Merriman TR. Evidence of interaction of CARD8 rs2043211 with NALP3 rs35829419 in Crohn’s disease. Genes Immun. 2043;201011:351–356. doi: 10.1038/gene.2010.11. [DOI] [PubMed] [Google Scholar]
- [4].Villani AC, Lemire M, Fortin G, Louis E, Silverberg MS, Collette C, et al. Common variants in the NLRP3 region contribute to Crohn’s disease susceptibility. Nat Genet. 2009;41:71–76. doi: 10.1038/ng.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [5].Cummings JR, Cooney RM, Clarke G, Beckly J, Geremia A, Pathan S, et al. The genetics of NOD-like receptors in Crohn’s disease. Tissue Antigens. 2010;76:48–56. doi: 10.1111/j.1399-0039.2010.01470.x. [DOI] [PubMed] [Google Scholar]
- [6].Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464:1357–1361. doi: 10.1038/nature08938. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [7].Kastbom A, Verma D, Eriksson P, Skogh T, Wingren G, Soderkvist P. Genetic variation in proteins of the cryopyrin inflammasome influences susceptibility and severity of rheumatoid arthritis (the Swedish TIRA project) Rheumatology (Oxford) 2008;47:415–417. doi: 10.1093/rheumatology/kem372. [DOI] [PubMed] [Google Scholar]
- [8].Richard KL, Filali M, Prefontaine P, Rivest S. Toll-like receptor 2 acts as a natural innate immune receptor to clear amyloid beta 1–42 and delay the cognitive decline in a mouse model of Alzheimer’s disease. J Neurosci. 2008;28:5784–5793. doi: 10.1523/JNEUROSCI.1146-08.2008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9].Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol. 2008;9:857–865. doi: 10.1038/ni.1636. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [10].Holley MM, Kielian T. Th1 and Th17 cells regulate innate immune responses and bacterial clearance during central nervous system infection. J Immunol. 2012;188:1360–1370. doi: 10.4049/jimmunol.1101660. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [11].Hoegen T, Tremel N, Klein M, Angele B, Wagner H, Kirschning C, et al. The NLRP3 inflammasome contributes to brain injury in pneumococcal meningitis and is activated through ATP-dependent lysosomal cathepsin B release. J Immunol. 2011;187:5440–5451. doi: 10.4049/jimmunol.1100790. [DOI] [PubMed] [Google Scholar]
- [12].Koedel U, Rupprecht T, Angele B, Heesemann J, Wagner H, Pfister HW, et al. MyD88 is required for mounting a robust host immune response to Streptococcus pneumoniae in the CNS. Brain. 2004;127:1437–1445. doi: 10.1093/brain/awh171. [DOI] [PubMed] [Google Scholar]
- [13].Jha S, Srivastava SY, Brickey WJ, Iocca H, Toews A, Morrison JP, et al. The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18. J Neurosci. 2010;30:15811–15820. doi: 10.1523/JNEUROSCI.4088-10.2010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [14].Griffin WS, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, et al. Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci U S A. 1989;86:7611–7615. doi: 10.1073/pnas.86.19.7611. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [15].Lee CY, Landreth GE. The role of microglia in amyloid clearance from the AD brain. J Neural Transm. 2010;117:949–960. doi: 10.1007/s00702-010-0433-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [16].Mustafa MM, Lebel MH, Ramilo O, Olsen KD, Reisch JS, Beutler B, et al. Correlation of interleukin-1 beta and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis. J Pediatr. 1989;115:208–213. doi: 10.1016/S0022-3476(89)80067-8. [DOI] [PubMed] [Google Scholar]
- [17].Fassbender K, Mielke O, Bertsch T, Muehlhauser F, Hennerici M, Kurimoto M, et al. Interferon-gamma-inducing factor (IL-18) and interferon-gamma in inflammatory CNS diseases. Neurology. 1999;53:1104–1106. doi: 10.1212/WNL.53.5.1104. [DOI] [PubMed] [Google Scholar]
- [18].Quagliarello VJ, Wispelwey B, Long WJ, Jr, Scheld WM. Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat. Characterization and comparison with tumor necrosis factor. J Clin Invest. 1991;87:1360–1366. doi: 10.1172/JCI115140. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [19].Zwijnenburg PJ, van der Poll T, Florquin S, Roord JJ, Van Furth AM. IL-1 receptor type 1 gene-deficient mice demonstrate an impaired host defense against pneumococcal meningitis. J Immunol. 2003;170:4724–4730. doi: 10.4049/jimmunol.170.9.4724. [DOI] [PubMed] [Google Scholar]
- [20].Koedel U, Winkler F, Angele B, Fontana A, Flavell RA, Pfister HW. Role of Caspase-1 in experimental pneumococcal meningitis: Evidence from pharmacologic Caspase inhibition and Caspase-1-deficient mice. Ann Neurol. 2002;51:319–329. doi: 10.1002/ana.10103. [DOI] [PubMed] [Google Scholar]
- [21].Scott JR. Scrapie pathogenesis. Br Med Bull. 1993;49:778–791. doi: 10.1093/oxfordjournals.bmb.a072646. [DOI] [PubMed] [Google Scholar]
- [22].Prusiner SB. Molecular biology of prion diseases. Science. 1991;252:1515–1522. doi: 10.1126/science.1675487. [DOI] [PubMed] [Google Scholar]
- [23].Hafner-Bratkovic I, Bencina M, Fitzgerald KA, Golenbock D, Jerala R. NLRP3 inflammasome activation in macrophage cell lines by prion protein fibrils as the source of IL-1beta and neuronal toxicity. Cell Mol Life Sci. 2012;69:4215–4228. doi: 10.1007/s00018-012-1140-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [24].Mathews RJ, Sprakes MB, McDermott MF. NOD-like receptors and inflammation. Arthritis Res Ther. 2008;10:228. doi: 10.1186/ar2525. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [25].Shenoy AR, Wellington DA, Kumar P, Kassa H, Booth CJ, Cresswell P, et al. GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals. Science. 2012;336:481–485. doi: 10.1126/science.1217141. [DOI] [PubMed] [Google Scholar]
- [26].Masumoto J, Taniguchi S, Ayukawa K, Sarvotham H, Kishino T, Niikawa N, et al. ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells. J Biol Chem. 1999;274:33835–33838. doi: 10.1074/jbc.274.48.33835. [DOI] [PubMed] [Google Scholar]
- [27].Stutz A, Golenbock DT, Latz E. Inflammasomes: too big to miss. J Clin Invest. 2009;119:3502–3511. doi: 10.1172/JCI40599. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [28].Stehlik C, Lee SH, Dorfleutner A, Stassinopoulos A, Sagara J, Reed JC. Apoptosis-associated speck-like protein containing a caspase recruitment domain is a regulator of procaspase-1 activation. J Immunol. 2003;171:6154–6163. doi: 10.4049/jimmunol.171.11.6154. [DOI] [PubMed] [Google Scholar]
- [29].Martinon F, Tschopp J. Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ. 2007;14:10–22. doi: 10.1038/sj.cdd.4402038. [DOI] [PubMed] [Google Scholar]
- [30].Martinon F. Detection of immune danger signals by NALP3. J Leukoc Biol. 2008;83:507–511. doi: 10.1189/jlb.0607362. [DOI] [PubMed] [Google Scholar]
- [31].Mayor A, Martinon F, De Smedt T, Petrilli V, Tschopp J. A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses. Nat Immunol. 2007;8:497–503. doi: 10.1038/ni1459. [DOI] [PubMed] [Google Scholar]
- [32].Hu Y, Mao K, Zeng Y, Chen S, Tao Z, Yang C, et al. Tripartitemotif protein 30 negatively regulates NLRP3 inflammasome activation by modulating reactive oxygen species production. J Immunol. 2010;185:7699–7705. doi: 10.4049/jimmunol.1001099. [DOI] [PubMed] [Google Scholar]
- [33].Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock KL, et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008;9:847–856. doi: 10.1038/ni.1631. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [34].Bruchard M, Mignot G, Derangere V, Chalmin F, Chevriaux A, Vegran F, et al. Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth. Nat Med. 2013;19:57–64. doi: 10.1038/nm.2999. [DOI] [PubMed] [Google Scholar]
- [35].Allen IC, Scull MA, Moore CB, Holl EK, McElvania-TeKippe E, Taxman DJ, et al. The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity. 2009;30:556–565. doi: 10.1016/j.immuni.2009.02.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [36].Owen DM, Gale M., Jr. Fighting the flu with inflammasome signaling. Immunity. 2009;30:476–478. doi: 10.1016/j.immuni.2009.03.011. [DOI] [PubMed] [Google Scholar]
- [37].Gross O, Poeck H, Bscheider M, Dostert C, Hannesschlager N, Endres S, et al. Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature. 2009;459:433–436. doi: 10.1038/nature07965. [DOI] [PubMed] [Google Scholar]
- [38].Barlan AU, Griffin TM, McGuire KA, Wiethoff CM. Adenovirus membrane penetration activates the NLRP3 inflammasome. J Virol. 2011;85:146–155. doi: 10.1128/JVI.01265-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [39].Pontillo A, Silva LT, Oshiro TM, Finazzo C, Crovella S, Duarte AJ. HIV-1 induces NALP3-inflammasome expression and interleukin-1beta secretion in dendritic cells from healthy individuals but not from HIV-positive patients. AIDS. 2012;26:11–18. doi: 10.1097/QAD.0b013e32834d697f. [DOI] [PubMed] [Google Scholar]
- [40].Munoz-Planillo R, Franchi L, Miller LS, Nunez G. A critical role for hemolysins and bacterial lipoproteins in Staphylococcus aureus-induced activation of the Nlrp3 inflammasome. J Immunol. 2009;183:3942–3948. doi: 10.4049/jimmunol.0900729. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [41].Joly S, Ma N, Sadler JJ, Soll DR, Cassel SL, Sutterwala FS. Cutting edge: Candida albicans hyphae formation triggers activation of the Nlrp3 inflammasome. J Immunol. 2009;183:3578–3581. doi: 10.4049/jimmunol.0901323. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [42].Yu M, Levine SJ. Toll-like receptor, RIG-I-like receptors and the NLRP3 inflammasome: key modulators of innate immune responses to double-stranded RNA viruses. Cytokine Growth Factor Rev. 2011;22:63–72. doi: 10.1016/j.cytogfr.2011.02.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [43].Franchi L, Eigenbrod T, Nunez G. Cutting edge: TNF-alpha mediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation. J Immunol. 2009;183:792–796. doi: 10.4049/jimmunol.0900173. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [44].Aimanianda V, Haensler J, Lacroix-Desmazes S, Kaveri SV, Bayry J. Novel cellular and molecular mechanisms of induc tion of immune responses by aluminum adjuvants. Trends Pharmacol Sci. 2009;30:287–295. doi: 10.1016/j.tips.2009.03.005. [DOI] [PubMed] [Google Scholar]
- [45].Dostert C, Petrilli V. Asbestos triggers inflammation by activating the Nalp3 inflammasome. Med Sci (Paris) 2008;24:916–918. doi: 10.1051/medsci/20082411916. [DOI] [PubMed] [Google Scholar]
- [46].Harris J, Sharp FA, Lavelle EC. The role of inflammasomes in the immunostimulatory effects of particulate vaccine adjuvants. Eur J Immunol. 2010;40:634–638. doi: 10.1002/eji.200940172. [DOI] [PubMed] [Google Scholar]
- [47].Li H, Ambade A, Re F. Cutting edge: Necrosis activates the NLRP3 inflammasome. J Immunol. 2009;183:1528–1532. doi: 10.4049/jimmunol.0901080. [DOI] [PubMed] [Google Scholar]
- [48].Mariathasan S, Weiss DS, Newton K, McBride J, O’Rourke K, Roose-Girma M, et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature. 2006;440:228–232. doi: 10.1038/nature04515. [DOI] [PubMed] [Google Scholar]
- [49].Liu-Bryan R. Intracellular innate immunity in gouty arthritis: role of NALP3 inflammasome. Immunol Cell Biol. 2010;88:20–23. doi: 10.1038/icb.2009.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [50].Yamasaki K, Muto J, Taylor KR, Cogen AL, Audish D, Bertin J, et al. NLRP3/cryopyrin is necessary for interleukin-1beta (IL-1beta) release in response to hyaluronan, an endogenous trigger of inflammation in response to injury. J Biol Chem. 2009;284:12762–12771. doi: 10.1074/jbc.M806084200. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [51].Petrilli V, Papin S, Dostert C, Mayor A, Martinon F, Tschopp J. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ. 2007;14:1583–1589. doi: 10.1038/sj.cdd.4402195. [DOI] [PubMed] [Google Scholar]
- [52].Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature. 2011;469:221–225. doi: 10.1038/nature09663. [DOI] [PubMed] [Google Scholar]
- [53].Shimada K, Crother TR, Karlin J, Dagvadorj J, Chiba N, Chen S, et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity. 2012;36:401–414. doi: 10.1016/j.immuni.2012.01.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [54].Pelegrin P, Surprenant A. Pannexin-1 couples to maitotoxinand nigericin-induced interleukin-1beta release through a dye uptake-independent pathway. J Biol Chem. 2007;282:2386–2394. doi: 10.1074/jbc.M610351200. [DOI] [PubMed] [Google Scholar]
- [55].de Rivero Vaccari JP, Bastien D, Yurcisin G, Pineau I, Dietrich WD, De Koninck Y, et al. P2X4 receptors influence inflammasome activation after spinal cord injury. J Neurosci. 2012;32:3058–3066. doi: 10.1523/JNEUROSCI.4930-11.2012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [56].Marina-Garcia N, Franchi L, Kim YG, Miller D, McDonald C, Boons GJ, et al. Pannexin-1-mediated intracellular delivery of muramyl dipeptide induces caspase-1 activation via cryopyrin/NLRP3 independently of Nod2. J Immunol. 2008;180:4050–4057. doi: 10.4049/jimmunol.180.6.4050. [DOI] [PubMed] [Google Scholar]
- [57].Lemasters JJ, Theruvath TP, Zhong Z, Nieminen AL. Mitochondrial calcium and the permeability transition in cell death. Biochim Biophys Acta. 2009;1787:1395–1401. doi: 10.1016/j.bbabio.2009.06.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [58].Murakami T, Ockinger J, Yu J, Byles V, McColl A, Hofer AM, et al. Critical role for calcium mobilization in activation of the NLRP3 inflammasome. Proc Natl Acad Sci U S A. 2012;109:11282–11287. doi: 10.1073/pnas.1117765109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [59].Lee GS, Subramanian N, Kim AI, Aksentijevich I, Goldbach-Mansky R, Sacks DB, et al. The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP. Nature. 2012;492:123–127. doi: 10.1038/nature11588. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [60].Cassel SL, Eisenbarth SC, Iyer SS, Sadler JJ, Colegio OR, Tephly LA, et al. The Nalp3 inflammasome is essential for the development of silicosis. Proc Natl Acad Sci U S A. 2008;105:9035–9040. doi: 10.1073/pnas.0803933105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [61].Tschopp J, Schroder K. NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production? Nat Rev Immunol. 2010;10:210–215. doi: 10.1038/nri2725. [DOI] [PubMed] [Google Scholar]
- [62].Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. Thioredoxininteracting protein links oxidative stress to inflammasome activation. Nat Immunol. 2010;11:136–140. doi: 10.1038/ni.1831. [DOI] [PubMed] [Google Scholar]
- [63].Schroder K, Zhou R, Tschopp J. The NLRP3 inflammasome: a sensor for metabolic danger? Science. 2010;327:296–300. doi: 10.1126/science.1184003. [DOI] [PubMed] [Google Scholar]
- [64].Bryan NB, Dorfleutner A, Kramer SJ, Yun C, Rojanasakul Y, Stehlik C. Differential splicing of the apoptosis-associated speck like protein containing a caspase recruitment domain (ASC) regulates inflammasomes. J Inflamm (Lond) 2010;7:23. doi: 10.1186/1476-9255-7-23. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [65].Stehlik C, Dorfleutner A. COPs and POPs: modulators of inflammasome activity. J Immunol. 2007;179:7993–7998. doi: 10.4049/jimmunol.179.12.7993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [66].Young JL, Sukhova GK, Foster D, Kisiel W, Libby P, Schonbeck U. The serpin proteinase inhibitor 9 is an endogenous inhibitor of interleukin 1beta-converting enzyme (caspase-1) activity in human vascular smooth muscle cells. J Exp Med. 2000;191:1535–1544. doi: 10.1084/jem.191.9.1535. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [67].Saitoh T, Fujita N, Jang MH, Uematsu S, Yang BG, Satoh T, et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature. 2008;456:264–268. doi: 10.1038/nature07383. [DOI] [PubMed] [Google Scholar]
- [68].Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, Lam HC, et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol. 2011;12:222–230. doi: 10.1038/ni.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [69].Guarda G, Braun M, Staehli F, Tardivel A, Mattmann C, Forster I, et al. Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity. 2011;34:213–223. doi: 10.1016/j.immuni.2011.02.006. [DOI] [PubMed] [Google Scholar]
- [70].Guarda G, Dostert C, Staehli F, Cabalzar K, Castillo R, Tardivel A, et al. T cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes. Nature. 2009;460:269–273. doi: 10.1038/nature08100. [DOI] [PubMed] [Google Scholar]
- [71].Hanamsagar R, Torres V, Kielian T. Inflammasome activation and IL-1beta/IL-18 processing are influenced by distinct pathways in microglia. J Neurochem. 2011;119:736–748. doi: 10.1111/j.1471-4159.2011.07481.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [72].Lin LF, Liao MJ, Xue XY, Zhang W, Yan L, Cai L, et al. Com bination of Abeta clearance and neurotrophic factors as a potential treatment for Alzheimer’s disease. Neurosci Bull. 2013;29:111–120. doi: 10.1007/s12264-012-1287-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [73].Marella M, Chabry J. Neurons and astrocytes respond to prion infection by inducing microglia recruitment. J Neurosci. 2004;24:620–627. doi: 10.1523/JNEUROSCI.4303-03.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [74].Rock RB, Gekker G, Hu S, Sheng WS, Cheeran M, Lokensgard JR, et al. Role of microglia in central nervous system infections. Clin Microbiol Rev. 2004;17:942–964. doi: 10.1128/CMR.17.4.942-964.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [75].Tribouillard-Tanvier D, Striebel JF, Peterson KE, Chesebro B. Analysis of protein levels of 24 cytokines in scrapie agent-infected brain and glial cell cultures from mice differing in prion protein expression levels. J Virol. 2009;83:11244–11253. doi: 10.1128/JVI.01413-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [76].Shi F, Yang L, Kouadir M, Yang Y, Wang J, Zhou X, et al. The NALP3 inflammasome is involved in neurotoxic prion peptideinduced microglial activation. J Neuroinflamm. 2012;9:73. doi: 10.1186/1742-2094-9-73. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [77].Inoue M, Williams KL, Gunn MD, Shinohara ML. NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2012;109:10480–10485. doi: 10.1073/pnas.1201836109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [78].Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med. 2006;355:581–592. doi: 10.1056/NEJMoa055137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [79].Hoffman HM, Throne ML, Amar NJ, Sebai M, Kivitz AJ, Kavanaugh A, et al. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 2008;58:2443–2452. doi: 10.1002/art.23687. [DOI] [PubMed] [Google Scholar]
- [80].Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, et al. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009;360:2416–2425. doi: 10.1056/NEJMoa0810787. [DOI] [PubMed] [Google Scholar]
- [81].Lamkanfi M, Mueller JL, Vitari AC, Misaghi S, Fedorova A, Deshayes K, et al. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J Cell Biol. 2009;187:61–70. doi: 10.1083/jcb.200903124. [DOI] [PMC free article] [PubMed] [Google Scholar]