The Inflammasome Pyrin Contributes to Pertussis Toxin-Induced IL-1β Synthesis, Neutrophil Intravascular Crawling and Autoimmune Encephalomyelitis
Microbial agents can aggravate inflammatory diseases, such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). An example is pertussis toxin (PTX), which is used to promote EAE by an obscure mechanism. We have reported that PTX triggers an IL-6-mediated signaling cascade that increases the number of leukocytes that patrol the vasculature by crawling on its luminal surface. We show here that PTX, through its ADP-ribosyltransferase activity, induces: 1) TLR4 signaling in myeloid cells, leading to pro-IL-1β synthesis; and 2) a pyrin-dependent inflammasome that cleaves pro-IL-1β into its active form. Then, IL-1β stimulates nearby stromal cells to secrete IL-6. Without pyrin, PTX does not induce neutrophil adhesion to cerebral capillaries and is less effective at inducing EAE in mice with encephalitogenic T lymphocytes. This study identifies the first microbial molecule that activates pyrin, a mechanism by which infections may influence MS and a potential therapeutic target for immune disorders.
Vyšlo v časopise:
The Inflammasome Pyrin Contributes to Pertussis Toxin-Induced IL-1β Synthesis, Neutrophil Intravascular Crawling and Autoimmune Encephalomyelitis. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004150
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004150
Souhrn
Microbial agents can aggravate inflammatory diseases, such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). An example is pertussis toxin (PTX), which is used to promote EAE by an obscure mechanism. We have reported that PTX triggers an IL-6-mediated signaling cascade that increases the number of leukocytes that patrol the vasculature by crawling on its luminal surface. We show here that PTX, through its ADP-ribosyltransferase activity, induces: 1) TLR4 signaling in myeloid cells, leading to pro-IL-1β synthesis; and 2) a pyrin-dependent inflammasome that cleaves pro-IL-1β into its active form. Then, IL-1β stimulates nearby stromal cells to secrete IL-6. Without pyrin, PTX does not induce neutrophil adhesion to cerebral capillaries and is less effective at inducing EAE in mice with encephalitogenic T lymphocytes. This study identifies the first microbial molecule that activates pyrin, a mechanism by which infections may influence MS and a potential therapeutic target for immune disorders.
Zdroje
1. AscherioA, MungerKL, LunemannJD (2012) The initiation and prevention of multiple sclerosis. Nat Rev Neurol 8: 602–612.
2. KochMW, MetzLM, AgrawalSM, YongVW (2013) Environmental factors and their regulation of immunity in multiple sclerosis. J Neurol Sciol 324: 10–612.
3. MarrieRA, WolfsonC, SturkenboomMC, GoutO, HeinzlefO, et al. (2000) Multiple sclerosis and antecedent infections: a case-control study.sclerosis. NeurologySciol 54: 2307–2310.
4. HernanMA, ZhangSM, LipworthL, OlekMJ, AscherioA (2001) Multiple sclerosis and age at infection with common viruses. study.sclerosis. Epidemiologyol 12: 301–610.
5. GoldacreMJ, WottonCJ, SeagroattV, YeatesD (2004) Multiple sclerosis after infectious mononucleosis: record linkage study.osis. J Epidemiol Community Health 58: 1032–1050.
6. ThackerEL, MirzaeiF, AscherioA (2006) Infectious mononucleosis and risk for multiple sclerosis: a meta-analysis.is. Ann Neurol 59: 499–503.
7. NielsenTR, RostgaardK, NielsenNM, Koch-HenriksenN, HaahrS, et al. (2007) Multiple sclerosis after infectious mononucleosis.erosis: a meta-analysis.is. Arch Neurol 64: 72–5503.
8. AscherioA, MungerKL (2007) Environmental risk factors for multiple sclerosis. Part I: the role of infection. Ann Neuroll 61: 288–993.
9. ZaadstraBM, ChorusAM, van BuurenS, KalsbeekH, van NoortJM (2008) Selective association of multiple sclerosis with infectious mononucleosis.ection. Mult Sclerl 14: 307–133.
10. RamagopalanSV, ValdarW, DymentDA, DeLucaGC, YeeIM, et al. (2009) Association of infectious mononucleosis with multiple sclerosis. A population-based study. Neuroepidemiology 32: 257–623.
11. HandelAE, WilliamsonAJ, DisantoG, HandunnetthiL, GiovannoniG, et al. (2010) An updated meta-analysis of risk of multiple sclerosis following infectious mononucleosis. PLoS One 5: e12496.
12. SibleyWA, BamfordCR, ClarkK (1985) Clinical viral infections and multiple sclerosiserosis following infectious mononucleosis. Lancet 1: 1313–1353.
13. AndersenO, LygnerPE, BergstromT, AnderssonM, VahlneA (1993) Viral infections trigger multiple sclerosis relapses: a prospective seroepidemiological study. J Neurol 240: 417–223.
14. PanitchHS (1994) Influence of infection on exacerbations of multiple sclerosisective seroepidemiological study. Ann Neurol 36 SupplS25–823.
15. EdwardsS, ZvartauM, ClarkeH, IrvingW, BlumhardtLD (1998) Clinical relapses and disease activity on magnetic resonance imaging associated with viral upper respiratory tract infections in multiple sclerosis. J Neurol Neurosurg Psychiatry 64: 736–413.
16. BuljevacD, FlachHZ, HopWC, HijdraD, LamanJD, et al. (2002) Prospective study on the relationship between infections and multiple sclerosis exacerbations.er respiratory tract infections in multiple sclerosis. Brain 125: 952–603.
17. TremlettH, van der MeiIA, PittasF, BlizzardL, PaleyG, et al. (2008) Monthly ambient sunlight, infections and relapse rates in multiple sclerosis.is exacerbations.er respiratory tract infections in multiple sclerosis. Neuroepidemiology 31: 271–903.
18. MunzC, LunemannJD, GettsMT, MillerSD (2009) Antiviral immune responses: triggers of or triggered by autoimmunity? Nat Rev Immunolgy 9: 246–583.
19. KakalachevaK, MunzC, LunemannJD (2011) Viral triggers of multiple sclerosis.of or triggered by autoimmunity? Biochim Biophys Acta 1812: 132–403.
20. GovermanJ, WoodsA, LarsonL, WeinerLP, HoodL, et al. (1993) Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell 72: 551–603.
21. YokoteH, MiyakeS, CroxfordJL, OkiS, MizusawaH, et al. (2008) NKT cell-dependent amelioration of a mouse model of multiple sclerosis by altering gut flora.ous autoimmunity. Am J Pathol 173: 1714–1723.
22. LeeYK, MenezesJS, UmesakiY, MazmanianSK (2011) Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis.immunity. Proc Natl Acad Sci U S A 108 Suppl 14615–4622.
23. BererK, MuesM, KoutrolosM, RasbiZA, BozikiM, et al. (2011) Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination.lomyelitis.immunity. Nature 479: 538–412.
24. StromnesIM, GovermanJM (2006) Active induction of experimental allergic encephalomyelitis.gger autoimmune demyelination.lomyelitis.immunity. Nat Protoc 1: 1810–1892.
25. StromnesIM, GovermanJM (2006) Passive induction of experimental allergic encephalomyelitis.ger autoimmune demyelination.lomyelitis.immunity. Nat Protoc 1: 1952–1960.
26. CarbonettiNH (2010) Pertussis toxin and adenylate cyclase toxin: key virulence factors of Bordetella pertussis and cell biology tools. Future Microbiol 5: 455–690.
27. PlautRD, CarbonettiNHM (2008) Retrograde transport of pertussis toxin in the mammalian cell.tors of Bordetella pertussis and cell biology tools. Cell Microbiolol 10: 1130–1190.
28. BokochGM, KatadaT, NorthupJK, HewlettEL, GilmanAG (1983) Identification of the predominant substrate for ADP-ribosylation by islet activating protein.d cell biology tools. J Biol Chemiolol 258: 2072–2050.
29. CodinaJ, HildebrandtJ, IyengarR, BirnbaumerL, SekuraRD, et al. (1983) Pertussis toxin substrate, the putative Ni component of adenylyl cyclases, is an alpha beta heterodimer regulated by guanine nucleotide and magnesium. Proc Natl Acad Sci U S A 80: 4276–4280.
30. MangmoolS, KuroseH (2011) G(i/o) protein-dependent and -independent actions of Pertussis Toxin (PTX).is an alpha beta heterodimer regulated by guanine nucleotide and magnesium. Toxins (Basel) Sci U S A 3: 884–990.
31. KerfootSM, LongEM, HickeyMJ, AndoneguiG, LapointeBM, et al. (2004) TLR4 contributes to disease-inducing mechanisms resulting in central nervous system autoimmune diseaser regulated by guanine nucleotide and magnesium. J Immunol 173: 7070–7070.
32. RichardJF, RoyM, Audoy-RemusJ, TremblayP, VallieresL (2011) Crawling phagocytes recruited in the brain vasculature after pertussis toxin exposure through IL6, ICAM1, and ITGαM. guanine nucleotide and magnesium. Brain Pathol 21: 661–671.
33. RoyM, RichardJF, DumasA, VallieresL, P, VallieresL (2012) CXCL1 can be regulated by IL-6 and promotes granulocyte adhesion to brain capillaries during bacterial toxin exposure and encephalomyelitis.magnesium. J Neuroinflammation 9: 18.
34. AkiraS, UematsuS, TakeuchiO (2006) Pathogen recognition and innate immunity. Cell 124: 783–801.
35. TakeuchiO, AkiraS (2010) Pattern recognition receptors and inflammation. Cell 140: 805–201.
36. SchroderK, TschoppJ (2010) The inflammasomes. Cell 140: 821–321.
37. RathinamVA, VanajaSK, FitzgeraldKA (2012) Regulation of inflammasome signaling. Nat Immunol 13: 333–221.
38. LatzE, XiaoTS, StutzA, KA (2013) Activation and regulation of the inflammasomes. Nat Rev Immunol 13: 397–411.
39. RichardsN, SchanerP, DiazA, StuckeyJ, SheldenE, et al. (2001) Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis. J Biol Chemunol 276: 39320–39329.
40. YuJW, WuJ, ZhangZ, DattaP, IbrahimiI, et al. (2006) Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, via ASC oligomerization.ed apoptosis. Cell Death Differ 13: 236–499.
41. YuJW, Fernandes-AlnemriT, DattaP, WuJ, JulianaC, et al. (2007) Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants. Mol Cellth Differ 28: 214–279.
42. GavrilinMA, MitraS, SeshadriS, NateriJ, BerheF, et al. (2009) Pyrin critical to macrophage IL-1beta response to Francisella challenge.lammatory PSTPIP1 mutants. J Immunolh Differ 182: 7982–7999.
43. GavrilinMA, AbdelazizDH, MostafaM, AbdulrahmanBA, GrandhiJ, et al. (2012) Activation of the pyrin inflammasome by intracellular Burkholderia cenocepacia.ry PSTPIP1 mutants. J Immunolh Differ 188: 3469–3477.
44. YuJW, FariasA, HwangI, Fernandes-AlnemriT, AlnemriES (2013) Ribotoxic stress through p38 mitogen-activated protein kinase activates in vitro the human pyrin inflammasome. J Biol ChemDiffer 288(16): 11378–83.
45. ChaeJJ, KomarowHD, ChengJ, WoodG, RabenN, et al. (2003) Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis. Mol CellhemDiffer 11: 591–604.
46. ChaeJJ, WoodG, MastersSL, RichardK, ParkG, et al. (2006) The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production. Proc Natl Acad Sci U S A 103: 9982–9974.
47. PapinS, CueninS, AgostiniL, MartinonF, WernerS, et al. (2007) The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing. Cell Death Differi U S A 14: 1457–1466.
48. HeskerPR, NguyenM, KovarovaM, TingJP, KollerBH, et al. (2012) Genetic loss of murine pyrin, the Familial Mediterranean Fever protein, increases interleukin-1beta levels.ponents and inhibits proIL-1beta processing. PLoS One 7: e511056.
49. GowingG, VallieresL, JulienJP (2006) Mouse model for ablation of proliferating microglia in acute CNS injuries. Glia One 53: 331–756.
50. MatsushimaH, OgawaY, MiyazakiT, TanakaH, NishibuA, et al. (2010) Intravital imaging of IL-1beta production in skin.a in acute CNS injuries. J Invest Dermatol 130: 1571–1580.
51. PizzaM, CovacciA, BartoloniA, PeruginiM, NencioniL, et al. (1989) Mutants of pertussis toxin suitable for vaccine development. CNS injuries. Science 246: 497–500.
52. VallieresL, SawchenkoPE (2003) Bone marrow-derived cells that populate the adult mouse brain preserve their hematopoietic identity. J Neurosci 23: 5197–5207.
53. Audoy-RemusJ, RichardJF, SouletD, ZhouH, KubesP, et al. (2008) Rod-Shaped monocytes patrol the brain vasculature and give rise to perivascular macrophages under the influence of proinflammatory cytokines and angiopoietin-2. J Neurosci 28: 10187–10199.
54. CarlsonT, KroenkeM, RaoP, LaneTE, SegalB, P, etal (2008) The Th17-ELR+ CXC chemokine pathway is essential for the development of central nervous system autoimmune disease. proinflammatory cytokines and angiopoietin-2. J Exp Medi 205: 811–2399.
55. ChristyAL, WalkerME, HessnerMJ, BrownMAB (2013) Mast cell activation and neutrophil recruitment promotes early and robust inflammation in the meninges in EAE.ase. proinflammatory cytokines and angiopoietin-2. J Autoimmun 42: 50–61399.
56. SteinbachK, PiedaventM, BauerS, NeumannJT, FrieseMA (2013) Neutrophils Amplify Autoimmune Central Nervous System Infiltrates by Maturing Local APCs. the meninges in EAE.ase. proinflammatory cytokines and angiopoietin-2. J Immunolun 191(9): 4531–9.
57. BettelliE, PaganyM, WeinerHL, LiningtonC, SobelRA, et al. (2003) Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis.mmatory cytokines and angiopoietin-2. J Exp Medun 197: 1073–1819.
58. ChanJK, RothJ, OppenheimJJ, TraceyKJ, VoglT, et al. (2012) Alarmins: awaiting a clinical response. J Clin Invest 122: 2711–2919.
59. The International FMF Consortium (1997) Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 90: 797–8079.
60. French FMF Consortium Consortium (1997) A candidate gene for familial Mediterranean fever. Nat Genet 17: 25–31079.
61. BernotA, da SilvaC, PetitJL, CruaudC, CaloustianC, et al. (1998) Non-founder mutations in the MEFV gene establish this gene as the cause of familial Mediterranean fever (FMF). Hum Mol Genet 7: 1317–1259.
62. ShinarY, LivnehA, VillaY, PinhasovA, ZeitounI, et al. (2003) Common mutations in the familial Mediterranean fever gene associate with rapid progression to disability in non-Ashkenazi Jewish multiple sclerosis patients. Genes Immunet 4: 197–2039.
63. UnalA, DursunA, EmreU, TascilarNF, AnkaraliHI, et al. (2010) Evaluation of common mutations in the Mediterranean fever gene in Multiple Sclerosis patients: is it a susceptibility gene?ewish multiple sclerosis patients. J Neurol Scit 294: 38–42039.
64. YahalomG, KivityS, LidarM, Vaknin-DembinskyA, KarussisD, et al. (2011) Familial Mediterranean fever (FMF) and multiple sclerosis: an association study in one of the world's largest FMF cohorts?ewish multiple sclerosis patients. Eur J Neurolt 18: 1146–1509.
65. KumpfelT, GerdesLA, WackerT, BlaschekA, HavlaJ, et al. (2012) Familial Mediterranean fever-associated mutation pyrin E148Q as a potential risk factor for multiple sclerosis.MF cohorts?ewish multiple sclerosis patients. Mult Sclerolt 18: 1229–1389.
66. MaattaJA, SjoholmUR, NygardasPT, SalmiAA, HinkkanenAE (1998) Neutrophils secreting tumor necrosis factor alpha infiltrate the central nervous system of BALB/c mice with experimental autoimmune encephalomyelitis.tients. J Neuroimmunol 90: 162–7589.
67. ReiseterBS, MillerGT, HappMP, KasaianMT (1998) Treatment of murine experimental autoimmune encephalomyelitis with a myelin basic protein peptide analog alters the cellular composition of leukocytes infiltrating the cerebrospinal fluid. J Neuroimmunol 91: 156–7089.
68. TranEH, PrinceEN, OwensT, MP, KasaianMT (2000) IFN-gamma shapes immune invasion of the central nervous system via regulation of chemokines. J Immunolmunol 164: 2759–2689.
69. ReddyJ, WaldnerH, ZhangX, IllesZ, WucherpfennigKW, et al. (2005) Cutting edge: CD4+CD25+ regulatory T cells contribute to gender differences in susceptibility to experimental autoimmune encephalomyelitis. J Immunolmunol 175: 5591–5589.
70. KroenkeMA, CarlsonTJ, AndjelkovicAV, SegalBM, KW, SobelRA, et al. (2008) IL-12- and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition. J Exp Medmunol 205: 1535–1419.
71. SoulikaAM, LeeE, McCauleyE, MiersL, BannermanP, et al. (2009) Initiation and progression of axonopathy in experimental autoimmune encephalomyelitis.S chemokine profile, and response to cytokine inhibition. J Neurosciunol 29: 14965–14979.
72. WuF, CaoW, YangY, LiuA (2010) Extensive infiltration of neutrophils in the acute phase of experimental autoimmune encephalomyelitis in C57BL/6 mice.e to cytokine inhibition. Histochem Cell Biol 133: 313–2279.
73. KangZ, AltuntasCZ, GulenMF, LiuC, GiltiayN, et al. (2010) Astrocyte-restricted ablation of interleukin-17-induced Act1-mediated signaling ameliorates autoimmune encephalomyelitis.o cytokine inhibition. Immunity 32: 414–2579.
74. McCollSR, StaykovaMA, WozniakA, FordhamS, BruceJ, et al. (1998) Treatment with anti-granulocyte antibodies inhibits the effector phase of experimental autoimmune encephalomyelitis.itis.o cytokine inhibition. J Immunol 161: 6421–6679.
75. LiuL, DarnallL, HuT, ChoiK, LaneTE, et al. (2010) Myelin repair is accelerated by inactivating CXCR2 on nonhematopoietic cells.erimental autoimmune encephalomyelitis.itis.o cytokine inhibition. J Neurosci 30: 9074–9839.
76. SaadounS, WatersP, MacDonaldC, BellBA, VincentA, et al. (2012) Neutrophil protease inhibition reduces neuromyelitis optica-immunoglobulin G-induced damage in mouse brain.myelitis.itis.o cytokine inhibition. Ann Neurol 71: 323–3339.
77. NaegeleM, TillackK, ReinhardtS, SchipplingS, MartinR, et al. (2012) Neutrophils in multiple sclerosis are characterized by a primed phenotype. G-induced damage in mouse brain.myelitis.itis.o cytokine inhibition. J Neuroimmunol 242: 60–71339.
78. LundBT, AshikianN, TaHQ, ChakryanY, ManoukianK, et al. (2004) Increased CXCL8 (IL-8) expression in Multiple Sclerosis. J Neuroimmunol 155: 161–7139.
79. BangsSC, McMichaelAJ, XuXN (2006) Bystander T cell activation—implications for HIV infection and other diseases. Trends Immunol 27: 518–2439.
80. GijbelsK, BrockeS, AbramsJS, SteinmanL (1995) Administration of neutralizing antibodies to interleukin-6 (IL-6) reduces experimental autoimmune encephalomyelitis and is associated with elevated levels of IL-6 bioactivity in central nervous system and circulation. Mol MedImmunol 1: 795–8059.
81. SamoilovaEB, HortonJL, HilliardB, LiuTS, ChenY (1998) IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: roles of IL-6 in the activation and differentiation of autoreactive T cells.f IL-6 bioactivity in central nervous system and circulation. J Immunolmunol 161: 6480–6659.
82. OkudaY, SakodaS, BernardCC, FujimuraH, SaekiY, et al. (1998) IL-6-deficient mice are resistant to the induction of experimental autoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein.ive T cells.f IL-6 bioactivity in central nervous system and circulation. Int Immunolnol 10: 703–8659.
83. EugsterHP, FreiK, KopfM, LassmannH, FontanaAY, et al. (1998) IL-6-deficient mice resist myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. Eur J Immunoll 28: 2178–2879.
84. OkudaY, SakodaS, FujimuraH, SaekiY, KishimotoT, et al. (1999) IL-6 plays a crucial role in the induction phase of myelin oligodendrocyte glucoprotein 35–55 induced experimental autoimmune encephalomyelitis. J Neuroimmunol 101: 188–9679.
85. ArimaY, HaradaM, KamimuraD, ParkJH, KawanoF, et al. (2012) Regional neural activation defines a gateway for autoreactive T cells to cross the blood-brain barrier.xperimental autoimmune encephalomyelitis. Cell 148: 447–5779.
86. VeldhoenM, HockingRJ, AtkinsCJ, LocksleyRM, StockingerB (2006) TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells.oimmune encephalomyelitis. Immunity 24: 179–8979.
87. BettelliE, CarrierY, GaoW, KornT, StromTB, et al. (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells.ucing T cells.oimmune encephalomyelitis. Naturety 441: 235–8979.
88. ManganPR, HarringtonLE, O'QuinnDB, HelmsWS, BullardDC, et al. (2006) Transforming growth factor-beta induces development of the T(H)17 lineage.r TH17 and regulatory T cells.ucing T cells.oimmune encephalomyelitis. Naturety 441: 231–4979.
89. SeradaS, FujimotoM, MiharaM, KoikeN, OhsugiY, et al. (2008) IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis.omyelitis. Proc Natl Acad Sci U S A 105: 9041–9679.
90. OguraH, MurakamiM, OkuyamaY, TsuruokaM, KitabayashiC, et al. (2008) Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction. autoimmune encephalomyelitis.omyelitis. Immunity 29: 628–3679.
91. ZhaoL, TangY, YouZ, WangQ, LiangS, et al. (2011) Interleukin-17 contributes to the pathogenesis of autoimmune hepatitis through inducing hepatic interleukin-6 expression.halomyelitis.omyelitis. PLoS One 6: e1890979.
92. RichardsN, SchanerP, DiazA, StuckeyJ, SheldenE, et al. (2001) Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis.interleukin-6 expression.halomyelitis.omyelitis. J Biol Chem 276: 39320–39399.
93. ShohamNG, CentolaM, MansfieldE, HullKM, WoodG, et al. (2003) Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway.itis.omyelitis. Proc Natl Acad Sci U S A 100: 13501–13569.
94. PapinS, CueninS, AgostiniL, MartinonF, WernerS, et al. (2007) The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing. Cell Death Differi U S A 14: 1457–1669.
95. Luu-TheV, PaquetN, CalvoE, CumpsJ (2005) Improved real-time RT-PCR method for high-throughput measurements using second derivative calculation and double correction.its proIL-1beta processing. Biotechniquesfferi U S A 38: 287–9369.
96. VilleneuveJ, TremblayP, VallieresL (2005) Tumor necrosis factor reduces brain tumor growth by enhancing macrophage recruitment and microcyst formation.ble correction.its proIL-1beta processing. Cancer Res 65: 3928–3369.
97. BouchardC, PageJ, BedardA, TremblayP, VallieresL (2007) G protein-coupled receptor 84, a microglia-associated protein expressed in neuroinflammatory conditionsation.ble correction.its proIL-1beta processing. Glia 55: 790–8009.
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