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Role of Inflammasome in Chronic Kidney Disease

  • Liang Li
  • Wei Tang
  • Fan YiEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1165)

Abstract

The inflammasome is a multiprotein complex assembled by intracytoplasmic pattern recognition receptors and is a key component of the innate immune system for host defense. Inflammasome recruits and activates the proinflammatory protease caspase-1 by recognizing pathogen-associated molecular patterns (PAMPs) or host-derived damage-associated molecular patterns (DAMPs). Activated caspase-1 cleaves the precursors of IL-1β and IL-18 to produce the corresponding mature cytokines. Several types of inflammasomes have been identified, such as NLRP3, NLRP1, IPAF (NLRC4) and AIM2. NLRP3 has recently been reported as a central pathogenic mechanism of chronic kidney disease (CKD). In this chapter, we briefly summarize the current knowledge about the roles of inflammasomes in the pathogenesis of CKD. A better understanding of the function of inflammasomes will provide unexpected opportunities to develop new therapies for kidney diseases by modulation of the innate immune system.

Keywords

Inflammasome Chronic kidney disease Pattern recognition receptors Inflammation Fibrosis 

References

  1. Abais JM, Zhang C, Xia M, Liu Q, Gehr TW, Boini KM et al (2013) NADPH oxidase-mediated triggering of inflammasome activation in mouse podocytes and glomeruli during hyperhomocysteinemia. Antioxid Redox Signal 18:1537–1548CrossRefGoogle Scholar
  2. Bakker PJ, Butter LM, Kors L, Teske GJ, Aten J, Sutterwala FS et al (2014) Nlrp3 is a key modulator of diet-induced nephropathy and renal cholesterol accumulation. Kidney Int 85:1112–1122CrossRefGoogle Scholar
  3. Boini KM, Xia M, Abais JM, Li G, Pitzer AL, Gehr TW et al (2014) Activation of inflammasomes in podocyte injury of mice on the high fat diet: effects of ASC gene deletion and silencing. Biochim Biophys Acta 1843:836–845CrossRefGoogle Scholar
  4. Boyden ED, Dietrich WF (2006) Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat Genet 38:240–244CrossRefGoogle Scholar
  5. Broderick L, De Nardo D, Franklin BS, Hoffman HM, Latz E (2015) The inflammasomes and autoinflammatory syndromes. Annu Rev Pathol 10:395–424CrossRefGoogle Scholar
  6. Caruso R, Warner N, Inohara N, Nunez G (2014) NOD1 and NOD2: signaling, host defense, and inflammatory disease. Immunity 41:898–908CrossRefGoogle Scholar
  7. Cavalca V, Cighetti G, Bamonti F, Loaldi A, Bortone L, Novembrino C et al (2001) Oxidative stress and homocysteine in coronary artery disease. Clin Chem 47:887–892PubMedGoogle Scholar
  8. Chen K, Zhang J, Zhang W, Zhang J, Yang J, Li K et al (2013) ATP-P2X4 signaling mediates NLRP3 inflammasome activation: a novel pathway of diabetic nephropathy. Int J Biochem Cell Biol 45:932–943CrossRefGoogle Scholar
  9. Conley SM, Abais JM, Boini KM, Li PL (2017) Inflammasome activation in chronic glomerular diseases. Curr Drug Targets 18:1019–1029CrossRefGoogle Scholar
  10. Conway EM (2012) Thrombomodulin and its role in inflammation. Semin Immunopathol 34:107–125CrossRefGoogle Scholar
  11. Du P, Fan B, Han H, Zhen J, Shan J, Wang X et al (2013) NOD2 promotes renal injury by exacerbating inflammation and podocyte insulin resistance in diabetic nephropathy. Kidney Int 84:265–276CrossRefGoogle Scholar
  12. Duncan JA, Canna SW (2018) The NLRC4 inflammasome. Immunol Rev 281:115–123CrossRefGoogle Scholar
  13. El-Nahas AM (2003) Plasticity of kidney cells: role in kidney remodeling and scarring. Kidney Int 64:1553–1563CrossRefGoogle Scholar
  14. Emmerson BT, Cross M, Osborne JM, Axelsen RA (1990) Reaction of MDCK cells to crystals of monosodium urate monohydrate and uric acid. Kidney Int 37:36–43CrossRefGoogle Scholar
  15. Fang L, Xie D, Wu X, Cao HD, Su WF, Yang JW (2013) Involvement of endoplasmic reticulum stress in albuminuria induced inflammasome activation in renal proximal tubular cells. PLoS ONE 8:e72344CrossRefGoogle Scholar
  16. Faustin B, Lartigue L, Bruey JM, Luciano F, Sergienko E, Bailly-Maitre B et al (2007) Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Mol Cell 25:713–724CrossRefGoogle Scholar
  17. Fernandes-Alnemri T, Yu JW, Juliana C, Solorzano L, Kang S, Wu J et al (2010) The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nat Immunol 11:385–393CrossRefGoogle Scholar
  18. Fritz JH, Ferrero RL, Philpott DJ, Girardin SE (2006) Nod-like proteins in immunity, inflammation and disease. Nat Immunol 7:1250–1257CrossRefGoogle Scholar
  19. Gao P, Meng XF, Su H, He FF, Chen S, Tang H et al (2014) Thioredoxin-interacting protein mediates NALP3 inflammasome activation in podocytes during diabetic nephropathy. Biochim Biophys Acta 1843:2448–2460CrossRefGoogle Scholar
  20. Granata S, Dalla Gassa A, Bellin G, Lupo A, Zaza G (2016) Transcriptomics: a step behind the comprehension of the polygenic influence on oxidative stress, immune deregulation, and mitochondrial dysfunction in chronic kidney disease. Biomed Res Int 2016:9290857PubMedPubMedCentralGoogle Scholar
  21. Gu J, Liu G, Xing J, Song H, Wang Z (2018) Fecal bacteria from Crohn’s disease patients more potently activated NOD-like receptors and Toll-like receptors in macrophages, in an IL-4-repressible fashion. Microb Pathog 121:40–44CrossRefGoogle Scholar
  22. Han H, Wang Y, Li X, Wang PA, Wei X, Liang W et al (2013) Novel role of NOD2 in mediating Ca2+ signaling: evidence from NOD2-regulated podocyte TRPC6 channels in hyperhomocysteinemia. Hypertension 62:506–511CrossRefGoogle Scholar
  23. Hara S, Kamei D, Sasaki Y, Tanemoto A, Nakatani Y, Murakami M (2010) Prostaglandin E synthases: understanding their pathophysiological roles through mouse genetic models. Biochimie 92:651–659CrossRefGoogle Scholar
  24. He L, Peng X, Liu G, Tang C, Liu H, Liu F et al (2015) Anti-inflammatory effects of triptolide on IgA nephropathy in rats. Immunopharmacol Immunotoxicol 37:421–427CrossRefGoogle Scholar
  25. Hu B, Jin C, Li HB, Tong J, Ouyang X, Cetinbas NM et al (2016) The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury. Science 354:765–768CrossRefGoogle Scholar
  26. Hutton HL, Ooi JD, Holdsworth SR, Kitching AR (2016) The NLRP3 inflammasome in kidney disease and autoimmunity. Nephrology 21:736–744CrossRefGoogle Scholar
  27. Iwasaki T, Kaneko N, Ito Y, Takeda H, Sawasaki T, Heike T et al (2016) Nod2-Nodosome in a cell-free system: implications in pathogenesis and drug discovery for blau syndrome and early-onset sarcoidosis. Sci World J 2016:2597376CrossRefGoogle Scholar
  28. Kanwar YS, Sun L, Xie P, Liu FY, Chen S (2011) A glimpse of various pathogenetic mechanisms of diabetic nephropathy. Annu Rev Pathol 6:395–423CrossRefGoogle Scholar
  29. Ke B, Shen W, Fang X, Wu Q (2018) The NLPR3 inflammasome and obesity-related kidney disease. J Cell Mol Med 22:16–24CrossRefGoogle Scholar
  30. Keestra-Gounder AM, Tsolis RM (2017) NOD1 and NOD2: beyond peptidoglycan sensing. Trends Immunol 38:758–767CrossRefGoogle Scholar
  31. Kim YK, Shin JS, Nahm MH (2016) NOD-like receptors in infection, immunity, and diseases. Yonsei Med J 57:5–14CrossRefGoogle Scholar
  32. Knauf F, Asplin JR, Granja I, Schmidt IM, Moeckel GW, David RJ et al (2013) NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy. Kidney Int 84:895–901CrossRefGoogle Scholar
  33. Komada T, Chung H, Lau A, Platnich JM, Beck PL, Benediktsson H et al (2018) Macrophage uptake of necrotic cell DNA activates the AIM2 inflammasome to regulate a proinflammatory phenotype in CKD. J Am Soc Nephrol 29:1165–1181CrossRefGoogle Scholar
  34. Komada T, Usui F, Shirasuna K, Kawashima A, Kimura H, Karasawa T et al (2014) ASC in renal collecting duct epithelial cells contributes to inflammation and injury after unilateral ureteral obstruction. Am J Pathol 184:1287–1298CrossRefGoogle Scholar
  35. Kovesdy CP, Furth SL, Zoccali C (2017) Obesity and kidney disease: hidden consequences of the epidemic. Braz J Med Res 50:e6075Google Scholar
  36. Kurts C (2013) A crystal-clear mechanism of chronic kidney disease. Kidney Int 84:859–861CrossRefGoogle Scholar
  37. Lichtnekert J, Kulkarni OP, Mulay SR, Rupanagudi KV, Ryu M, Allam R et al (2011) Anti-GBM glomerulonephritis involves IL-1 but is independent of NLRP3/ASC inflammasome-mediated activation of caspase-1. PLoS ONE 6:e26778CrossRefGoogle Scholar
  38. Liu D, Xu M, Ding LH, Lv LL, Liu H, Ma KL et al (2014) Activation of the Nlrp3 inflammasome by mitochondrial reactive oxygen species: a novel mechanism of albumin-induced tubulointerstitial inflammation. Int J Biochem 57:7–19CrossRefGoogle Scholar
  39. Luo R, Kakizoe Y, Wang F, Fan X, Hu S, Yang T et al (2017) Deficiency of mPGES-1 exacerbates renal fibrosis and inflammation in mice with unilateral ureteral obstruction. Am J Physiol Renal Physiol 312:F121–F133CrossRefGoogle Scholar
  40. Ma Q (2013) Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 53:401–426CrossRefGoogle Scholar
  41. Magalhaes JG, Sorbara MT, Girardin SE, Philpott DJ (2011) What is new with nods? Curr Opin Immunol 23:29–34CrossRefGoogle Scholar
  42. Man SM, Karki R, Malireddi RK, Neale G, Vogel P, Yamamoto M et al (2015) The transcription factor IRF1 and guanylate-binding proteins target activation of the AIM2 inflammasome by Francisella infection. Nat Immunol 16:467–475CrossRefGoogle Scholar
  43. Martinon F (2010) Signaling by ROS drives inflammasome activation. Eur J Immunol 40:616–619CrossRefGoogle Scholar
  44. Mestecky J, Raska M, Julian BA, Gharavi AG, Renfrow MB, Moldoveanu Z et al (2013) IgA nephropathy: molecular mechanisms of the disease. Annu Rev Pathol 8:217–240CrossRefGoogle Scholar
  45. Monk D, Sanchez-Delgado M, Fisher R (2017) NLRPs, the subcortical maternal complex and genomic imprinting. Reproduction 154:R161–R170CrossRefGoogle Scholar
  46. Mulay SR, Anders HJ (2017) Crystal nephropathies: mechanisms of crystal-induced kidney injury. Nat Rev Nephrol 13:226–240CrossRefGoogle Scholar
  47. Mulay SR, Desai J, Kumar SV, Eberhard JN, Thomasova D, Romoli S et al (2016) Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis. Nat Commun 7:10274CrossRefGoogle Scholar
  48. Mulay SR, Evan A, Anders HJ (2014) Molecular mechanisms of crystal-related kidney inflammation and injury Implications for cholesterol embolism, crystalline nephropathies and kidney stone disease. Nephrol Dial Transplant 29:507–514CrossRefGoogle Scholar
  49. Mulay SR, Kulkarni OP, Rupanagudi KV, Migliorini A, Darisipudi MN, Vilaysane A et al (2013) Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1beta secretion. J Clin Invest 123:236–246CrossRefGoogle Scholar
  50. Nakagawa N, Yuhki K, Kawabe J, Fujino T, Takahata O, Kabara M et al (2012) The intrinsic prostaglandin E2-EP4 system of the renal tubular epithelium limits the development of tubulointerstitial fibrosis in mice. Kidney Int 82:158–171CrossRefGoogle Scholar
  51. Okla M, Zaher W, Alfayez M, Chung S (2018) Inhibitory effects of toll-like Receptor 4, NLRP3 inflammasome, and interleukin-1beta on white adipocyte browning. Inflammation 41:626–642CrossRefGoogle Scholar
  52. Pulskens WP, Butter LM, Teske GJ, Claessen N, Dessing MC, Flavell RA et al (2014) Nlrp3 prevents early renal interstitial edema and vascular permeability in unilateral ureteral obstruction. PLoS ONE 9:e85775CrossRefGoogle Scholar
  53. Shahzad K, Bock F, Dong W, Wang H, Kopf S, Kohli S et al (2015) Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy. Kidney Int 87:74–84CrossRefGoogle Scholar
  54. Shen HH, Yang YX, Meng X, Luo XY, Li XM, Shuai ZW et al (2018) NLRP3: a promising therapeutic target for autoimmune diseases. Autoimmun Rev 17:694–702CrossRefGoogle Scholar
  55. Shigeoka AA, Kambo A, Mathison JC, King AJ, Hall WF, da Silva Correia J et al (2010) Nod1 and nod2 are expressed in human and murine renal tubular epithelial cells and participate in renal ischemia reperfusion injury. J Immunol 184:2297–2304CrossRefGoogle Scholar
  56. Soares JLS, Fernandes FP, Patente TA, Monteiro MB, Parisi MC, Giannella-Neto D et al (2018) Gain-of-function variants in NLRP1 protect against the development of diabetic kidney disease: NLRP1 inflammasome role in metabolic stress sensing? Clin Immunol 187:46–49CrossRefGoogle Scholar
  57. Sogawa Y, Nagasu H, Iwase S, Ihoriya C, Itano S, Uchida A et al (2017) Infiltration of M1, but not M2, macrophages is impaired after unilateral ureter obstruction in Nrf2-deficient mice. Sci Rep 7:8801CrossRefGoogle Scholar
  58. Song ZH, Ji ZN, Lo CK, Dong TT, Zhao KJ, Li OT et al (2004) Chemical and biological assessment of a traditional chinese herbal decoction prepared from Radix Astragali and Radix Angelicae Sinensis: orthogonal array design to optimize the extraction of chemical constituents. Planta Med 70:1222–1227CrossRefGoogle Scholar
  59. Tsai YL, Hua KF, Chen A, Wei CW, Chen WS, Wu CY et al (2017) NLRP3 inflammasome: pathogenic role and potential therapeutic target for IgA nephropathy. Sci Rep 7:41123CrossRefGoogle Scholar
  60. Vilaysane A, Chun J, Seamone ME, Wang W, Chin R, Hirota S et al (2010) The NLRP3 inflammasome promotes renal inflammation and contributes to CKD. J Am Soc Nephrol 21:1732–1744CrossRefGoogle Scholar
  61. Wang X, Yi F (2015) Implication of pattern-recognition receptors in cardiovascular diseases. Antioxid Redox Signal 22:1130–1145CrossRefGoogle Scholar
  62. Wong DWL, Yiu WH, Chan KW, Li Y, Li B, Lok SWY et al (2018) Activated renal tubular Wnt/beta-catenin signaling triggers renal inflammation during overload proteinuria. Kidney Int 93:1367–1383CrossRefGoogle Scholar
  63. Yang SM, Ka SM, Hua KF, Wu TH, Chuang YP, Lin YW et al (2013) Antroquinonol mitigates an accelerated and progressive IgA nephropathy model in mice by activating the Nrf2 pathway and inhibiting T cells and NLRP3 inflammasome. Free Radic Bio Med 61:285–297CrossRefGoogle Scholar
  64. Yu G, Bai Z, Chen Z, Chen H, Wang G, Wang G et al (2017) The NLRP3 inflammasome is a potential target of ozone therapy aiming to ease chronic renal inflammation in chronic kidney disease. Int Immunopharmacol 43:203–209CrossRefGoogle Scholar
  65. Yu HH, Chiang BL (2014) Diagnosis and classification of IgA nephropathy. Autoimmun Rev 13:556–559CrossRefGoogle Scholar
  66. Zhang C, Boini KM, Xia M, Abais JM, Li X, Liu Q et al (2012) Activation of Nod-like receptor protein 3 inflammasomes turns on podocyte injury and glomerular sclerosis in hyperhomocysteinemia. Hypertension 60:154–162CrossRefGoogle Scholar
  67. Zhang L, Wang XZ, Li YS, Zhang L, Hao LR (2017) Icariin ameliorates IgA nephropathy by inhibition of nuclear factor kappa b/Nlrp3 pathway. FEBS Open Bio 7:54–63CrossRefGoogle Scholar
  68. Zhang W, Cai Y, Xu W, Yin Z, Gao X, Xiong S (2013) AIM2 facilitates the apoptotic DNA-induced systemic lupus erythematosus via arbitrating macrophage functional maturation. J Clin Immunol 33:925–937CrossRefGoogle Scholar
  69. Zhao C, Gillette DD, Li X, Zhang Z, Wen H (2014) Nuclear factor E2-related factor-2 (Nrf2) is required for NLRP3 and AIM2 inflammasome activation. J Biol Chem 289:17020–17029CrossRefGoogle Scholar
  70. Zhao J, Zhang H, Huang Y, Wang H, Wang S, Zhao C et al (2013) Bay11-7082 attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-κB activation. Int Immunopharmacol 17:116–122CrossRefGoogle Scholar
  71. Zheng L, Zhang J, Yuan X, Tang J, Qiu S, Peng Z et al (2018) Fluorofenidone attenuates interleukin-1β production by interacting with NLRP3 inflammasome in unilateral ureteral obstruction. Nephrology 23:573–584CrossRefGoogle Scholar
  72. Zhou M, Tang W, Fu Y, Xu X, Wang Z, Lu Y et al (2015) Progranulin protects against renal ischemia/reperfusion injury in mice. Kidney Int 87:918–929CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Pharmacology, School of Basic Medical SciencesShandong UniversityJinanChina
  2. 2.Department of Pathogenic Biology, Basic Medical SciencesShandong UniversityJinanChina

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