An update on the role of the inflammasomes in the pathogenesis of kidney diseases

Pediatric Nephrology

Volumn 31, Issue 4, 2016, Pages 535-544

  Darisipudi, Murthy N ^a   Knauf, Felix ^a,b  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Acute kidney injury; Chronic kidney disease; Crystals; Inflammasomes; Kidney; Microbiome

Indexed keywords

INFLAMMASOME; NOD LIKE RECEPTOR P3; NOD LIKE RECEPTOR P6; NUCLEOTIDE BINDING OLIGOMERIZATION DOMAIN LIKE RECEPTOR; UNCLASSIFIED DRUG; CRYOPYRIN;

ACUTE KIDNEY FAILURE; CALCIUM OXALATE STONE; CHRONIC KIDNEY DISEASE; DISEASE COURSE; HOMEOSTASIS; HOST RESISTANCE; HUMAN; INTESTINE; INTESTINE FLORA; KIDNEY DISEASE; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; ANIMAL; CHRONIC KIDNEY FAILURE; IMMUNOLOGY; INNATE IMMUNITY; KIDNEY; METABOLISM; MICROBIOLOGY; NEPHROLITHIASIS; SIGNAL TRANSDUCTION;

ACUTE KIDNEY INJURY; ANIMALS; GASTROINTESTINAL MICROBIOME; HUMANS; IMMUNITY, INNATE; INFLAMMASOMES; INTESTINES; KIDNEY; KIDNEY CALCULI; NLR FAMILY, PYRIN DOMAIN-CONTAINING 3 PROTEIN; RENAL INSUFFICIENCY, CHRONIC; SIGNAL TRANSDUCTION;

EID: 84959549937     PISSN: 0931041X     EISSN: 1432198X     Source Type: Journal    
DOI: 10.1007/s00467-015-3153-z     Document Type: Review

References (106)

1. Lech M, Grobmayr R, Ryu M, Lorenz G, Hartter I, Mulay SR, Susanti HE, Kobayashi KS, Flavell RA, Anders HJ (2014) Macrophage phenotype controls long-term AKI outcomes—kidney regeneration versus atrophy. J Am Soc Nephrol 25:292–304
2. Lamkanfi M, Dixit VM (2014) Mechanisms and functions of inflammasomes. Cell 157:1013–1022
3. Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10:417–426
4. Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, Speert D, Fernandes-Alnemri T, Wu J, Monks BG, Fitzgerald KA, Hornung V, Latz E (2009) Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol 183:787–791
5. Broderick L, De Nardo D, Franklin BS, Hoffman HM, Latz E (2015) The inflammasomes and autoinflammatory syndromes. Annu Rev Pathol 10:395–424
6. de Zoete MR, Palm NW, Zhu S, Flavell RA (2014) Inflammasomes. Cold Spring Harb Perspect Biol 6:a016287
7. Anders HJ, Muruve DA (2011) The inflammasomes in kidney disease. J Am Soc Nephrol 22:1007–1018
8. Leemans JC, Kors L, Anders HJ, Florquin S (2014) Pattern recognition receptors and the inflammasome in kidney disease. Nat Rev Nephrol 10:398–414
9. Anders HJ, Schaefer L (2014) Beyond tissue injury-damage-associated molecular patterns, toll-like receptors, and inflammasomes also drive regeneration and fibrosis. J Am Soc Nephrol 25:1387–1400
10. Zhuang Y, Hu C, Ding G, Zhang Y, Huang S, Jia Z, Zhang A (2015) Albumin impairs renal tubular tight junctions via targeting the NLRP3 inflammasome. Am J Physiol Renal Physiol 308:F1012–F1019
11. Abais JM, Xia M, Li G, Chen Y, Conley SM, Gehr TW, Boini KM, Li PL (2014) Nod-like receptor protein 3 (NLRP3) inflammasome activation and podocyte injury via thioredoxin-interacting protein (TXNIP) during hyperhomocysteinemia. J Biol Chem 289:27159–27168
12. Shahzad K, Bock F, Dong W, Wang H, Kopf S, Kohli S, Al-Dabet MM, Ranjan S, Wolter J, Wacker C, Biemann R, Stoyanov S, Reymann K, Soderkvist P, Gross O, Schwenger V, Pahernik S, Nawroth PP, Grone HJ, Madhusudhan T, Isermann B (2015) Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy. Kidney Int 87:74–84
13. Dong X, Swaminathan S, Bachman LA, Croatt AJ, Nath KA, Griffin MD (2007) Resident dendritic cells are the predominant TNF-secreting cell in early renal ischemia-reperfusion injury. Kidney Int 71:619–628
14. Kasimsetty SG, DeWolf SE, Shigeoka AA, McKay DB (2014) Regulation of TLR2 and NLRP3 in primary murine renal tubular epithelial cells. Nephron Clin Pract 127:119–123
15. Lorenz G, Darisipudi MN, Anders HJ (2014) Canonical and non-canonical effects of the NLRP3 inflammasome in kidney inflammation and fibrosis. Nephrol Dial Transplant 29:41–48
16. Homsi E, Janino P, de Faria JB (2006) Role of caspases on cell death, inflammation, and cell cycle in glycerol-induced acute renal failure. Kidney Int 69:1385–1392
17. Latz E (2010) The inflammasomes: mechanisms of activation and function. Curr Opin Immunol 22:28–33
18. Hornung V, Latz E (2010) Critical functions of priming and lysosomal damage for NLRP3 activation. Eur J Immunol 40:620–623
19. Wu H, Ma J, Wang P, Corpuz TM, Panchapakesan U, Wyburn KR, Chadban SJ (2010) HMGB1 contributes to kidney ischemia reperfusion injury. J Am Soc Nephrol 21:1878–1890
20. Duncan JA, Gao X, Huang MT, O'Connor BP, Thomas CE, Willingham SB, Bergstralh DT, Jarvis GA, Sparling PF, Ting JP (2009) Neisseria gonorrhoeae activates the proteinase cathepsin B to mediate the signaling activities of the NLRP3 and ASC-containing inflammasome. J Immunol 182:6460–6469
21. Rajan JV, Rodriguez D, Miao EA, Aderem A (2011) The NLRP3 inflammasome detects encephalomyocarditis virus and vesicular stomatitis virus infection. J Virol 85:4167–4172
22. Joly S, Ma N, Sadler JJ, Soll DR, Cassel SL, Sutterwala FS (2009) Cutting edge: Candida albicans hyphae formation triggers activation of the Nlrp3 inflammasome. J Immunol 183:3578–3581
23. Harder J, Franchi L, Munoz-Planillo R, Park JH, Reimer T, Nunez G (2009) Activation of the Nlrp3 inflammasome by Streptococcus pyogenes requires streptolysin O and NF-kappa B activation but proceeds independently of TLR signaling and P2X7 receptor. J Immunol 183:5823–5829
24. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440:237–241
25. Cassel SL, Eisenbarth SC, Iyer SS, Sadler JJ, Colegio OR, Tephly LA, Carter AB, Rothman PB, Flavell RA, Sutterwala FS (2008) The Nalp3 inflammasome is essential for the development of silicosis. Proc Natl Acad Sci USA 105:9035–9040
26. Dostert C, Petrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J (2008) Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320:674–677
27. Darisipudi MN, Thomasova D, Mulay SR, Brech D, Noessner E, Liapis H, Anders HJ (2012) Uromodulin triggers IL-1beta-dependent innate immunity via the NLRP3 inflammasome. J Am Soc Nephrol 23:1783–1789
28. Munoz-Planillo R, Kuffa P, Martinez-Colon G, Smith BL, Rajendiran TM, Nunez G (2013) K(+) efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 38:1142–1153
29. Lamkanfi M, Dixit VM (2012) Inflammasomes and their roles in health and disease. Annu Rev Cell Dev Biol 28:137–161
30. van Bruggen R, Koker MY, Jansen M, van Houdt M, Roos D, Kuijpers TW, van den Berg TK (2010) Human NLRP3 inflammasome activation is Nox1-4 independent. Blood 115:5398–5400
31. Jin C, Flavell RA (2010) Molecular mechanism of NLRP3 inflammasome activation. J Clin Immunol 30:628–631
32. Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, Fitzgerald KA, Latz E, Moore KJ, Golenbock DT (2008) The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol 9:857–865
33. Rock KL, Latz E, Ontiveros F, Kono H (2010) The sterile inflammatory response. Annu Rev Immunol 28:321–342
34. Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J (2010) Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol 11:136–140
35. Jin MS, Lee JO (2008) Structures of the toll-like receptor family and its ligand complexes. Immunity 29:182–191
36. Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S, Dong J, Newton K, Qu Y, Liu J, Heldens S, Zhang J, Lee WP, Roose-Girma M, Dixit VM (2011) Non-canonical inflammasome activation targets caspase-11. Nature 479:117–121
37. Kayagaki N, Wong MT, Stowe IB, Ramani SR, Gonzalez LC, Akashi-Takamura S, Miyake K, Zhang J, Lee WP, Muszynski A, Forsberg LS, Carlson RW, Dixit VM (2013) Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science 341:1246–1249
38. Vigano E, Mortellaro A (2013) Caspase-11: the driving factor for noncanonical inflammasomes. Eur J Immunol 43:2240–2245
39. Wang S, Miura M, Jung YK, Zhu H, Li E, Yuan J (1998) Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE. Cell 92:501–509
40. Broz P, Ruby T, Belhocine K, Bouley DM, Kayagaki N, Dixit VM, Monack DM (2012) Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1. Nature 490:288–291
41. Koyner JL, Garg AX, Thiessen-Philbrook H, Coca SG, Cantley LG, Peixoto A, Passik CS, Hong K, Parikh CR, TRIBE-AKI Consortium (2014) Adjudication of etiology of acute kidney injury: experience from the TRIBE-AKI multi-center study. BMC Nephrol 15:105
42. Doi K, Ishizu T, Tsukamoto-Sumida M, Hiruma T, Yamashita T, Ogasawara E, Hamasaki Y, Yahagi N, Nangaku M, Noiri E (2014) The high-mobility group protein B1-Toll-like receptor 4 pathway contributes to the acute lung injury induced by bilateral nephrectomy. Kidney Int 86:316–326
43. Zhao H, Perez JS, Lu K, George AJ, Ma D (2014) Role of Toll-like receptor-4 in renal graft ischemia-reperfusion injury. Am J Physiol Renal Physiol 306:F801–F811
44. Wu H, Chen G, Wyburn KR, Yin J, Bertolino P, Eris JM, Alexander SI, Sharland AF, Chadban SJ (2007) TLR4 activation mediates kidney ischemia/reperfusion injury. J Clin Invest 117:2847–2859
45. Kruger B, Krick S, Dhillon N, Lerner SM, Ames S, Bromberg JS, Lin M, Walsh L, Vella J, Fischereder M, Kramer BK, Colvin RB, Heeger PS, Murphy BT, Schroppel B (2009) Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation. Proc Natl Acad Sci USA 106:3390–3395
46. Wu H, Steenstra R, de Boer EC, Zhao CY, Ma J, van der Stelt JM, Chadban SJ (2014) Preconditioning with recombinant high-mobility group box 1 protein protects the kidney against ischemia–reperfusion injury in mice. Kidney Int 85:824–832
47. Allam R, Darisipudi MN, Tschopp J, Anders HJ (2013) Histones trigger sterile inflammation by activating the NLRP3 inflammasome. Eur J Immunol 43:3336–3342
48. Allam R, Scherbaum CR, Darisipudi MN, Mulay SR, Hagele H, Lichtnekert J, Hagemann JH, Rupanagudi KV, Ryu M, Schwarzenberger C, Hohenstein B, Hugo C, Uhl B, Reichel CA, Krombach F, Monestier M, Liapis H, Moreth K, Schaefer L, Anders HJ (2012) Histones from dying renal cells aggravate kidney injury via TLR2 and TLR4. J Am Soc Nephrol 23:1375–1388
49. Decleves AE, Caron N, Voisin V, Legrand A, Bouby N, Kultti A, Tammi MI, Flamion B (2012) Synthesis and fragmentation of hyaluronan in renal ischaemia. Nephrol Dial Transplant 27:3771–3781
50. Gao F, Koenitzer JR, Tobolewski JM, Jiang D, Liang J, Noble PW, Oury TD (2008) Extracellular superoxide dismutase inhibits inflammation by preventing oxidative fragmentation of hyaluronan. J Biol Chem 283:6058–6066
51. Ebid R, Lichtnekert J, Anders HJ (2014) Hyaluronan is not a ligand but a regulator of toll-like receptor signaling in mesangial cells: role of extracellular matrix in innate immunity. ISRN Nephrol 2014:714081
52. Iyer SS, Pulskens WP, Sadler JJ, Butter LM, Teske GJ, Ulland TK, Eisenbarth SC, Florquin S, Flavell RA, Leemans JC, Sutterwala FS (2009) Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc Natl Acad Sci USA 106:20388–20393
53. Shigeoka AA, Mueller JL, Kambo A, Mathison JC, King AJ, Hall WF, Correia Jda S, Ulevitch RJ, Hoffman HM, McKay DB (2010) An inflammasome-independent role for epithelial-expressed Nlrp3 in renal ischemia–reperfusion injury. J Immunol 185:6277–6285
54. Labbe K, McIntire CR, Doiron K, Leblanc PM, Saleh M (2011) Cellular inhibitors of apoptosis proteins cIAP1 and cIAP2 are required for efficient caspase-1 activation by the inflammasome. Immunity 35:897–907
55. Kim HJ, Lee DW, Ravichandran K, OK D, Akcay A, Nguyen Q, He Z, Jani A, Ljubanovic D, Edelstein CL (2013) NLRP3 inflammasome knockout mice are protected against ischemic but not cisplatin-induced acute kidney injury. J Pharmacol Exp Ther 346:465–472
56. Boyden ED, Dietrich WF (2006) Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat Genet 38:240–244
57. Faustin B, Lartigue L, Bruey JM, Luciano F, Sergienko E, Bailly-Maitre B, Volkmann N, Hanein D, Rouiller I, Reed JC (2007) Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Mol Cell 25:713–724
58. Rusai K, Huang H, Sayed N, Strobl M, Roos M, Schmaderer C, Heemann U, Lutz J (2008) Administration of interleukin-1 receptor antagonist ameliorates renal ischemia-reperfusion injury. Transplant Int 21:572–580
59. Dinarello CA, Simon A, van der Meer JW (2012) Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov 11:633–652
60. Dinarello CA (2011) Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 117:3720–3732
61. Rider P, Carmi Y, Guttman O, Braiman A, Cohen I, Voronov E, White MR, Dinarello CA, Apte RN (2011) IL-1alpha and IL-1beta recruit different myeloid cells and promote different stages of sterile inflammation. J Immunol 187:4835–4843
62. Xu D, Matsuo Y, Ma J, Koide S, Ochi N, Yasuda A, Funahashi H, Okada Y, Takeyama H (2010) Cancer cell-derived IL-1alpha promotes HGF secretion by stromal cells and enhances metastatic potential in pancreatic cancer cells. J Surg Oncol 102:469–477
63. Wolf JS, Chen Z, Dong G, Sunwoo JB, Bancroft CC, Capo DE, Yeh NT, Mukaida N, Van Waes C (2001) IL (interleukin)-1alpha promotes nuclear factor-kappaB and AP-1-induced IL-8 expression, cell survival, and proliferation in head and neck squamous cell carcinomas. Clin Cancer Res 7:1812–1820
64. Lee JW, Nam WJ, Han MJ, Shin JH, Kim JG, Kim SH, Kim HR, Oh DJ (2011) Role of IL-1alpha in cisplatin-induced acute renal failure in mice. Korean J Intern Med 26:187–194
65. Coccia M, Harrison OJ, Schiering C, Asquith MJ, Becher B, Powrie F, Maloy KJ (2012) IL-1beta mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4(+) Th17 cells. J Exp Med 209:1595–1609
66. Bersudsky M, Luski L, Fishman D, White RM, Ziv-Sokolovskaya N, Dotan S, Rider P, Kaplanov I, Aychek T, Dinarello CA, Apte RN, Voronov E (2014) Non-redundant properties of IL-1alpha and IL-1beta during acute colon inflammation in mice. Gut 63:598–609
67. Puri TS, Shakaib MI, Chang A, Mathew L, Olayinka O, Minto AW, Sarav M, Hack BK, Quigg RJ (2010) Chronic kidney disease induced in mice by reversible unilateral ureteral obstruction is dependent on genetic background. Am J Physiol Renal Physiol 298:F1024–F1032
68. Vilaysane A, Chun J, Seamone ME, Wang W, Chin R, Hirota S, Li Y, Clark SA, Tschopp J, Trpkov K, Hemmelgarn BR, Beck PL, Muruve DA (2010) The NLRP3 inflammasome promotes renal inflammation and contributes to CKD. J Am Soc Nephrol 21:1732–1744
69. Pulskens WP, Butter LM, Teske GJ, Claessen N, Dessing MC, Flavell RA, Sutterwala FS, Florquin S, Leemans JC (2014) Nlrp3 prevents early renal interstitial edema and vascular permeability in unilateral ureteral obstruction. PLoS One 9:e85775
70. Pulskens WP, Rampanelli E, Teske GJ, Butter LM, Claessen N, Luirink IK, van der Poll T, Florquin S, Leemans JC (2010) TLR4 promotes fibrosis but attenuates tubular damage in progressive renal injury. J Am Soc Nephrol 21:1299–1308
71. Chen K, Zhang J, Zhang W, Zhang J, Yang J, Li K, He Y (2013) ATP-P2X4 signaling mediates NLRP3 inflammasome activation: a novel pathway of diabetic nephropathy. Int J Biochem Cell Biol 45:932–943
72. Granata S, Masola V, Zoratti E, Scupoli MT, Baruzzi A, Messa M, Sallustio F, Gesualdo L, Lupo A, Zaza G (2015) NLRP3 inflammasome activation in dialyzed chronic kidney disease patients. PLoS One 10:e0122272
73. Martin-Rodriguez S, Caballo C, Gutierrez G, Vera M, Cruzado JM, Cases A, Escolar G, Diaz-Ricart M (2015) TLR4 and NALP3 inflammasome in the development of endothelial dysfunction in uraemia. Eur J Clin Invest 45:160–169
74. Herlitz LC, D'Agati VD, Markowitz GS (2012) Crystalline nephropathies. Arch Pathol Lab Med 136:713–720
75. Kurts C, Panzer U, Anders HJ, Rees AJ (2013) The immune system and kidney disease: basic concepts and clinical implications. Nat Rev Immunol 13:738–753
76. Jamal A, Ramzan A (2004) Renal and post-renal causes of acute renal failure in children. J Coll Physicians Surg Pak 14:411–415
77. Organ M, Norman RW (2011) Acute reversible kidney injury secondary to bilateral ureteric obstruction. Can Urol Assoc J 5:392–396
78. Gillen DL, Worcester EM, Coe FL (2005) Decreased renal function among adults with a history of nephrolithiasis: a study of NHANES III. Kidney Int 67:685–690
79. Colombaro V, Jadot I, Decleves AE, Voisin V, Giordano L, Habsch I, Malaisse J, Flamion B, Caron N (2015) Lack of hyaluronidases exacerbates renal post-ischemic injury, inflammation, and fibrosis. Kidney Int. doi:10.1038/ki.2015.53
80. Knauf F, Asplin JR, Granja I, Schmidt IM, Moeckel GW, David RJ, Flavell RA, Aronson PS (2013) NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy. Kidney Int 84:895–901
81. Knauf F, Ko N, Jiang Z, Robertson WG, Van Itallie CM, Anderson JM, Aronson PS (2011) Net intestinal transport of oxalate reflects passive absorption and SLC26A6-mediated secretion. J Am Soc Nephrol 22:2247–2255
82. Jiang Z, Asplin JR, Evan AP, Rajendran VM, Velazquez H, Nottoli TP, Binder HJ, Aronson PS (2006) Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6. Nat Genet 38:474–478
83. Ko N, Knauf F, Jiang Z, Markovich D, Aronson PS (2012) Sat1 is dispensable for active oxalate secretion in mouse duodenum. Am J Physiol Cell Physiol 303:C52–C57
84. Cochat P, Rumsby G (2013) Primary hyperoxaluria. N Engl J Med 369:649–658
85. Hueppelshaeuser R, von Unruh GE, Habbig S, Beck BB, Buderus S, Hesse A, Hoppe B (2012) Enteric hyperoxaluria, recurrent urolithiasis, and systemic oxalosis in patients with Crohn's disease. Pediatr Nephrol 27:1103–1109
86. Hoppe B, Langman CB (2003) A United States survey on diagnosis, treatment, and outcome of primary hyperoxaluria. Pediatr Nephrol 18:986–991
87. Mulay SR, Kulkarni OP, Rupanagudi KV, Migliorini A, Darisipudi MN, Vilaysane A, Muruve D, Shi Y, Munro F, Liapis H, Anders HJ (2013) Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1beta secretion. J Clin Invest 123:236–246
88. Kurts C (2013) A crystal-clear mechanism of chronic kidney disease. Kidney Int 84:859–861
89. Knoepfelmacher M, Rocha R, Salgado LR, Semer M, Voss D, Wajchenberg BL, Liberman B (1994) Nephropathic cystinosis: report of 2 cases and review of the literature. Rev Assoc Med Bras 40:43–46
90. Emma F, Nesterova G, Langman C, Labbe A, Cherqui S, Goodyer P, Janssen MC, Greco M, Topaloglu R, Elenberg E, Dohil R, Trauner D, Antignac C, Cochat P, Kaskel F, Servais A, Wuhl E, Niaudet P, Van't Hoff W, Gahl W, Levtchenko E (2014) Nephropathic cystinosis: an international consensus document. Nephrol Dial Transplant 29[Suppl 4]:iv87–iv94
91. Prencipe G, Caiello I, Cherqui S, Whisenant T, Petrini S, Emma F, De Benedetti F (2014) Inflammasome activation by cystine crystals: implications for the pathogenesis of cystinosis. J Am Soc Nephrol 25:1163–1169
92. Chevalier RL (2014) The proximal tubule in cystinosis: fight or flight? J Am Soc Nephrol 25:1131–1132
93. Coll RC, Robertson AA, Chae JJ, Higgins SC, Munoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A, Croker DE, Butler MS, Haneklaus M, Sutton CE, Nunez G, Latz E, Kastner DL, Mills KH, Masters SL, Schroder K, Cooper MA, O'Neill LA (2015) A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med 21:248–255
94. Grenier JM, Wang L, Manji GA, Huang WJ, Al-Garawi A, Kelly R, Carlson A, Merriam S, Lora JM, Briskin M, DiStefano PS, Bertin J (2002) Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF-kappaB and caspase-1. FEBS Lett 530:73–78
95. Mankan AK, Kubarenko A, Hornung V (2012) Immunology in clinic review series; focus on autoinflammatory diseases: inflammasomes: mechanisms of activation. Clin Exp Immunol 167:369–381
96. Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA, Booth CJ, Peaper DR, Bertin J, Eisenbarth SC, Gordon JI, Flavell RA (2011) NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145:745–757
97. Wlodarska M, Thaiss CA, Nowarski R, Henao-Mejia J, Zhang JP, Brown EM, Frankel G, Levy M, Katz MN, Philbrick WM, Elinav E, Finlay BB, Flavell RA (2014) NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. Cell 156:1045–1059
98. Lech M, Avila-Ferrufino A, Skuginna V, Susanti HE, Anders HJ (2010) Quantitative expression of RIG-like helicase, NOD-like receptor and inflammasome-related mRNAs in humans and mice. Int Immunol 22:717–728
99. Anand PK, Malireddi RK, Lukens JR, Vogel P, Bertin J, Lamkanfi M, Kanneganti TD (2012) NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature 488:389–393
100. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, Thaiss CA, Kau AL, Eisenbarth SC, Jurczak MJ, Camporez JP, Shulman GI, Gordon JI, Hoffman HM, Flavell RA (2012) Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482:179–185
101. Strowig T, Henao Mejia J, Elinav E, Flavell R (2012) Inflammasomes in health and disease. Nature 481:278–286
102. Anders HJ, Andersen K, Stecher B (2013) The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease. Kidney Int 83:1010–1016
103. Goncalves S, Pecoits-Filho R, Perreto S, Barberato SH, Stinghen AE, Lima EG, Fuerbringer R, Sauthier SM, Riella MC (2006) Associations between renal function, volume status and endotoxaemia in chronic kidney disease patients. Nephrol Dial Transplant 21:2788–2794
104. Szeto CC, Kwan BC, Chow KM, Lai KB, Chung KY, Leung CB, Li PK (2008) Endotoxemia is related to systemic inflammation and atherosclerosis in peritoneal dialysis patients. Clin J Am Soc Nephrol 3:431–436
105. Vaziri ND, Dure-Smith B, Miller R, Mirahmadi MK (1985) Pathology of gastrointestinal tract in chronic hemodialysis patients: an autopsy study of 78 cases. Am J Gastroenterol 80:608–611
106. Magnusson M, Magnusson KE, Sundqvist T, Denneberg T (1990) Increased intestinal permeability to differently sized polyethylene glycols in uremic rats: effects of low- and high-protein diets. Nephron 56:306–311