NF-ΚB in inflammation and renal diseases

Cell and Bioscience

Volumn 5, Issue 1, 2015, Pages

  Zhang, Haisong ^a   Sun, Shao Cong ^b,c  

^a HEBEI UNIVERSITY   (China)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^c UNIVERSITY OF TEXAS   (United States)

Author keywords

IgA nephropathy; Inflammation; Nephritis; NF B; Renal diseases

Indexed keywords

EID: 84960080303     PISSN: None     EISSN: 20453701     Source Type: Journal    
DOI: 10.1186/s13578-015-0056-4     Document Type: Review

References (155)

1. Sen R, Baltimore D. Inducibility of k immunoglobulin enhancer-binding protein NFkB by a posttranslational mechanism. Cell. 1986;47:921-8.
2. Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986;46:705-16.
3. Vallabhapurapu S, Karin M. Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol. 2009;27:693-733.
4. Hayden MS, Ghosh S. NF-kappaB, the first quarter-century: remarkable progress and outstanding questions. Genes Dev. 2012;26(3):203-34.
5. Zhang Y, Reinberg D. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev. 2001;15(18):2343-60.
6. Bohuslav J, Kravchenko VV, Parry GC, Erlich JH, Gerondakis S, Mackman N, et al. Regulation of an essential innate immune response by the p50 subunit of NF-kappaB. J Clin Invest. 1998;102(9):1645-52.
7. Wedel A, Frankenberger M, Sulski G, Petersmann I, Kuprash D, Nedospasov S, et al. Role of p52 (NF-kappaB2) in LPS tolerance in a human B cell line. Biol Chem. 1999;380(10):1193-9.
8. Carmody RJ, Ruan Q, Palmer S, Hilliard B, Chen YH. Negative regulation of toll-like receptor signaling by NF-kappaB p50 ubiquitination blockade. Science. 2007;317:875-8.
9. Bours V, Franzoso G, Azarenko V, Park S, Kanno T, Brown K, et al. The oncoprotein Bcl-3 directly transactivates through kB motifs via association with DNA-binding p50B homodimers. Cell. 1993;72:729-39.
10. Paz-Priel I, Houng S, Dooher J, Friedman AD. C/EBPalpha and C/EBPalpha oncoproteins regulate nfkb1 and displace histone deacetylases from NF-kappaB p50 homodimers to induce NF-kappaB target genes. Blood. 2011;117(15):4085-94.
11. Sun SC, Ley SC. New insights into NF-kappaB regulation and function. Trends Immunol. 2008;29:469-78.
12. Beinke S, Ley SC. Functions of NF-kappaB1 and NF-kappaB2 in immune cell biology. Biochem J. 2004;382:393-409.
13. Sun SC. Non-canonical NF-ΚB signaling pathway. Cell Res. 2011;21:71-85.
14. Sun SC. The noncanonical NF-kappaB pathway. Immunol Rev. 2012;246(1):125-40.
15. Gerondakis S, Grumont R, Gugasyan R, Wong L, Isomura I, Ho W, et al. Unravelling the complexities of the NF-kappaB signalling pathway using mouse knockout and transgenic models. Oncogene. 2006;25(51):6781-99.
16. Sun S-C, Ganchi PA, Ballard DW, Greene WC. NF-ΚB controls expression of inhibitor IkBa: evidence for an inducible autoregulatory pathway. Science. 1993;259:1912-5.
17. Peng B, Ling J, Lee AJ, Wang Z, Chang Z, Jin W, et al. Defective feedback regulation of NF-kappaB underlies Sjogren's syndrome in mice with mutated kappaB enhancers of the IkappaBalpha promoter. Proc Natl Acad Sci USA. 2010;107(34):15193-8.
18. Chen ZJ, Bhoj V, Seth RB. Ubiquitin, TAK1 and IKK: is there a connection? Cell Death Differ. 2006;13:687-92.
19. Liu S, Chen ZJ. Expanding role of ubiquitination in NF-ΚB signaling. Cell Res. 2011;21:6-21.
20. Reiley WW, Jin W, Lee AJ, Wright A, Wu X, Tewalt EF, et al. Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent kinase Tak1 and prevents abnormal T cell responses. J Exp Med. 2007;204:1475-85.
21. Tokunaga F. Linear ubiquitination-mediated NF-kappaB regulation and its related disorders. J Biochem. 2013;154(4):313-23.
22. Elton L, Carpentier I, Verhelst K, Staal J, Beyaert R. The multifaceted role of the E3 ubiquitin ligase HOIL-1: beyond linear ubiquitination. Immunol Rev. 2015;266(1):208-21.
23. Tokunaga F, Sakata S, Saeki Y, Satomi Y, Kirisako T, Kamei K, et al. Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation. Nat Cell Biol. 2009;11:123-32.
24. Haas TL, Emmerich CH, Gerlach B, Schmukle AC, Cordier SM, Rieser E, et al. Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. Mol Cell. 2009;36(5):831-44.
25. Rahighi S, Ikeda F, Kawasaki M, Akutsu M, Suzuki N, Kato R, et al. Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation. Cell. 2009;136(6):1098-109.
26. Gerlach B, Cordier SM, Schmukle AC, Emmerich CH, Rieser E, Haas TL, et al. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature. 2011;471(7340):591-6.
27. Sun SC. Deubiquitylation and regulation of the immune response. Nat Rev Immunol. 2008;8:501-11.
28. Sun SC. CYLD: a tumor suppressor deubiquitinase regulating NF-ΚB activation. Cell Death Differ. 2010;17:25-34.
29. Jin W, Reiley WR, Lee AJ, Wright A, Wu X, Zhang M, et al. Deubiquitinating enzyme CYLD regulates the peripheral development and naive phenotype maintenance of B cells. J Biol Chem. 2007;282:15884-93.
30. Komander D, Reyes-Turcu F, Licchesi JD, Odenwaelder P, Wilkinson KD, Barford D. Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains. EMBO Rep. 2009;10:466-73.
31. Harhaj EW, Dixit VM. Deubiquitinases in the regulation of NF-kappaB signaling. Cell Res. 2011;21(1):22-39.
32. Harhaj EW, Dixit VM. Regulation of NF-kappaB by deubiquitinases. Immunol Rev. 2012;246(1):107-24.
33. De A, Dainichi T, Rathinam CV, Ghosh S. The deubiquitinase activity of A20 is dispensable for NF-kappaB signaling. EMBO Rep. 2014;15(7):775-83.
34. Sun S-C, Ganchi PA, Beraud C, Ballard DW, Greene WC. Autoregulation of the NF-ΚB transactivator Rel A (p65) by multiple cytoplasmic inhibitors containing ankyrin motifs. Proc Natl Acad Sci USA. 1994;91:1346-50.
35. Senftleben U, Cao Y, Xiao G, Kraehn G, Greten F, Chen Y, et al. Activation of IKKa of a second, evolutionary conserved, NF-ΚB signaling pathway. Science. 2001;293:1495-9.
36. Xiao G, Harhaj EW, Sun SC. NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100. Mol Cell. 2001;7:401-9.
37. Liao G, Zhang M, Harhaj EW, Sun SC. Regulation of the NF-kappaB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. J Biol Chem. 2004;279(25):26243-50.
38. Hu H, Brittain GC, Chang JH, Puebla-Osorio N, Jin J, Zal A, et al. OTUD7B controls non-canonical NF-kappaB activation through deubiquitination of TRAF3. Nature. 2013;494(7437):371-4.
39. Jin J, Xiao Y, Chang JH, Yu J, Hu H, Starr R, et al. The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-kappaB signaling. Nat Immunol. 2012;13(11):1101-9.
40. Razani B, Zarnegar B, Ytterberg AJ, Shiba T, Dempsey PW, Ware CF, et al. Negative feedback in non-canonical NF-ΚB signaling modulates NIK stability through IKKα-mediated phosphorylation. Sci Sig. 2010;3(123):ra41.
41. Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454:428-35.
42. Ashley NT, Weil ZM, Nelson RJ. Inflammation: mechanisms, costs, and natural variation. Annu Rev Ecol Evol Syst. 2012;43:407-28.
43. Brubaker SW, Bonham KS, Zanoni I, Kagan JC. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol. 2015;33:257-90.
44. Tak PP, Firestein GS. NF-kappaB: a key role in inflammatory diseases. J Clin Invest. 2001;107(1):7-11.
45. O'Shea JJ, Paul WE. Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science. 2010;327(5969):1098-102.
46. Bartlett HS, Million RP. Targeting the IL-17-T(H)17 pathway. Nat Rev Drug Discov. 2015;14(1):11-2.
47. Lubberts E. The IL-23-IL-17 axis in inflammatory arthritis. Nat Rev Rheumatol. 2015;11(7):415-29.
48. Oh H, Ghosh S. NF-kappaB: roles and regulation in different CD4(+) T cell subsets. Immunol Rev. 2013;252(1):41-51.
49. Hilliard BA, Mason N, Xu L, Sun J, Lamhamedi-Cherradi SE, Liou HC, et al. Critical roles of c-Rel in autoimmune inflammation and helper T cell differentiation. J Clinic Invest. 2002;110:843-50.
50. Corn RA, Aronica MA, Zhang F, Tong Y, Stanley SA, Kim SR, et al. T cell-intrinsic requirement for NF-kappa B induction in postdifferentiation IFN-gamma production and clonal expansion in a Th1 response. J Immunol. 2003;171(4):1816-24.
51. Chen G, Hardy K, Pagler E, Ma L, Lee S, Gerondakis S, et al. The NF-kappaB transcription factor c-Rel is required for Th17 effector cell development in experimental autoimmune encephalomyelitis. J Immunol. 2011;187(9):4483-91.
52. Ruan Q, Kameswaran V, Zhang Y, Zheng S, Sun J, Wang J, et al. The Th17 immune response is controlled by the Rel-RORgamma-RORgamma T transcriptional axis. J Exp Med. 2011;208(11):2321-33.
53. Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol. 2009;9(8):556-67.
54. Gu C, Wu L, Li X. IL-17 family: cytokines, receptors and signaling. Cytokine. 2013;64(2):477-85.
55. Yu J, Zhou X, Nakaya M, Jin W, Cheng X, Sun SC. T Cell-intrinsic function of the noncanonical NF-kappaB pathway in the regulation of GM-CSF expression and experimental autoimmune encephalomyelitis. Pathogenesis. J Immunol. 2014;193(1):422-30.
56. Codarri L, Gyulveszi G, Tosevski V, Hesske L, Fontana A, Magnenat L, et al. RORgammat drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol. 2011;12(6):560-7.
57. El-Behi M, Ciric B, Dai H, Yan Y, Cullimore M, Safavi F, et al. The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol. 2011;12(6):568-75.
58. Imig JD, Ryan MJ. Immune and inflammatory role in renal disease. Compr Physiol. 2013;3(2):957-76.
59. Kurts C, Panzer U, Anders HJ, Rees AJ. The immune system and kidney disease: basic concepts and clinical implications. Nat Rev Immunol. 2013;13(10):738-53.
60. Anders HJ, Schlondorff D. Toll-like receptors: emerging concepts in kidney disease. Curr Opin Nephrol Hypertens. 2007;16(3):177-83.
61. Schroppel B, He JC. Expression of Toll-like receptors in the kidney: their potential role beyond infection. Kidney Int. 2006;69(5):785-7.
62. Lech M, Anders HJ. The pathogenesis of lupus nephritis. J Am Soc Nephrol JASN. 2013;24(9):1357-66.
63. Sterner RM, Hartono SP, Grande JP. The pathogenesis of lupus nephritis. J Clin Cell Immunol. 2014;5(2):205. doi: 10.4172/2155-9899.1000205.
64. Davidson A, Aranow C. Lupus nephritis: lessons from murine models. Nat Rev Rheumatol. 2010;6(1):13-20.
65. Bagavant H, Fu SM. Pathogenesis of kidney disease in systemic lupus erythematosus. Curr Opin Rheumatol. 2009;21(5):489-94.
66. Clynes R, Dumitru C, Ravetch JV. Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis. Science. 1998;279(5353):1052-4.
67. Turnberg D, Cook HT. Complement and glomerulonephritis: new insights. Curr Opin Nephrol Hypertens. 2005;14(3):223-8.
68. Kiryluk K, Novak J. The genetics and immunobiology of IgA nephropathy. J Clin Invest. 2014;124(6):2325-32.
69. Guijarro C, Egido J. Transcription factor-kappa B (NF-kappa B) and renal disease. Kidney Int. 2001;59(2):415-24.
70. Wardle EN. Nuclear factor kappaB for the nephrologist. Nephrol Dial Transpl Off Publ Eur Dial Transpl Assoc Eur Renal Assoc. 2001;16(9):1764-8.
71. Sanz AB, Sanchez-Nino MD, Ramos AM, Moreno JA, Santamaria B, Ruiz-Ortega M, et al. NF-kappaB in renal inflammation. J Am Soc Nephrol JASN. 2010;21(8):1254-62.
72. Yang CW, Wu MS, Pan MJ, Hong JJ, Yu CC, Vandewalle A, et al. Leptospira outer membrane protein activates NF-kappaB and downstream genes expressed in medullary thick ascending limb cells. J Am Soc Nephrol JASN. 2000;11(11):2017-26.
73. Donnahoo KK, Shames BD, Harken AH, Meldrum DR. Review article: the role of tumor necrosis factor in renal ischemia-reperfusion injury. J Urol. 1999;162(1):196-203.
74. Ruiz-Ortega M, Lorenzo O, Ruperez M, Konig S, Wittig B, Egido J. Angiotensin II activates nuclear transcription factor kappaB through AT(1) and AT(2) in vascular smooth muscle cells: molecular mechanisms. Circ Res. 2000;86(12):1266-72.
75. Ruiz-Ortega M, Ruperez M, Lorenzo O, Esteban V, Blanco J, Mezzano S, et al. Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney. Kidney Int Suppl. 2002;82:S12-22.
76. Arumugam S, Sreedhar R, Thandavarayan RA, Karuppagounder V, Krishnamurthy P, Suzuki K, et al. Angiotensin receptor blockers: Focus on cardiac and renal injury. Trends Cardiovasc Med. 2015;Epub ahead of print.
77. Ruiz-Ortega M, Bustos C, Hernandez-Presa MA, Lorenzo O, Plaza JJ, Egido J. Angiotensin II participates in mononuclear cell recruitment in experimental immune complex nephritis through nuclear factor-kappa B activation and monocyte chemoattractant protein-1 synthesis. J Immunol. 1998;161(1):430-9.
78. Ruiz-Ortega M, Lorenzo O, Ruperez M, Blanco J, Egido J. Systemic infusion of angiotensin II into normal rats activates nuclear factor-kappaB and AP-1 in the kidney: role of AT(1) and AT(2) receptors. Am J Pathol. 2001;158(5):1743-56.
79. Esteban V, Lorenzo O, Ruperez M, Suzuki Y, Mezzano S, Blanco J, et al. Angiotensin II, via AT1 and AT2 receptors and NF-kappaB pathway, regulates the inflammatory response in unilateral ureteral obstruction. J Am Soc Nephrol JASN. 2004;15(6):1514-29.
80. Duque N, Gomez-Guerrero C, Egido J. Interaction of IgA with Fc alpha receptors of human mesangial cells activates transcription factor nuclear factor-kappa B and induces expression and synthesis of monocyte chemoattractant protein-1, IL-8, and IFN-inducible protein 10. J Immunol. 1997;159(7):3474-82.
81. Coppo R, Amore A. Aberrant glycosylation in IgA nephropathy (IgAN). Kidney Int. 2004;65(5):1544-7.
82. Zhang F, Siow YL, O K. Hyperhomocysteinemia activates NF-kappaB and inducible nitric oxide synthase in the kidney. Kidney Int. 2004;65(4):1327-38.
83. Kumagai H, Katoh S, Hirosawa K, Kimura M, Hishida A, Ikegaya N. Renal tubulointerstitial injury in weanling rats with hyperhomocysteinemia. Kidney Int. 2002;62(4):1219-28.
84. Fischer PA, Dominguez GN, Cuniberti LA, Martinez V, Werba JP, Ramirez AJ, et al. Hyperhomocysteinemia induces renal hemodynamic dysfunction: is nitric oxide involved? J Am Soc Nephrol JASN. 2003;14(3):653-60.
85. Wang G, Siow YL, O K. Homocysteine stimulates nuclear factor kappaB activity and monocyte chemoattractant protein-1 expression in vascular smooth-muscle cells: a possible role for protein kinase C. Biochem J. 2000;352(Pt 3):817-26.
86. Wang G, Siow YL, OK. Homocysteine induces monocyte chemoattractant protein-1 expression by activating NF-kappaB in THP-1 macrophages. Am J Physiol Heart Circ Physiol. 2001;280(6):H2840-7.
87. Hussain S, Romio L, Saleem M, Mathieson P, Serrano M, Moscat J, et al. Nephrin deficiency activates NF-kappaB and promotes glomerular injury. J Am Soc Nephrol JASN. 2009;20(8):1733-43.
88. le Luong A, Fragiadaki M, Smith J, Boyle J, Lutz J, Dean JL, et al. Cezanne regulates inflammatory responses to hypoxia in endothelial cells by targeting TRAF6 for deubiquitination. Circ Res. 2013;112(12):1583-91.
89. Evans PC, Taylor ER, Coadwell J, Heyninck K, Beyaert R, Kilshaw PJ. Isolation and characterization of two novel A20-like proteins. Biochem J. 2001;357:617-23.
90. Panzer U, Steinmetz OM, Turner JE, Meyer-Schwesinger C, von Ruffer C, Meyer TN, et al. Resolution of renal inflammation: a new role for NF-kappaB1 (p50) in inflammatory kidney diseases. Am J Physiol Renal Physiol. 2009;297(2):F429-39.
91. Cao C, Wang S, Fan L, Wan X, Liu X, Chen X. Renal protection by ischemic preconditioning is associated with p50/p50 homodimers. Am J Nephrol. 2010;31(1):1-8.
92. Murugan R, Kellum JA. Acute kidney injury: what's the prognosis? Nat Rev Nephrol. 2011;7(4):209-17.
93. Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int. 2012;81(5):442-8.
94. Bonventre JV, Zuk A. Ischemic acute renal failure: an inflammatory disease? Kidney Int. 2004;66(2):480-5.
95. Volpini RA, Costa RS, da Silva CG, Coimbra TM. Inhibition of nuclear factor-kappaB activation attenuates tubulointerstitial nephritis induced by gentamicin. Nephron Physiol. 2004;98(4):p97-106.
96. Fujihara CK, Antunes GR, Mattar AL, Malheiros DM, Vieira JM Jr, Zatz R. Chronic inhibition of nuclear factor-kappaB attenuates renal injury in the 5/6 renal ablation model. Am J Physiol Renal Physiol. 2007;292(1):F92-9.
97. Ding W, Yang L, Zhang M, Gu Y. Chronic inhibition of nuclear factor kappa B attenuates aldosterone/salt-induced renal injury. Life Sci. 2012;90(15-16):600-6.
98. Wan X, Fan L, Hu B, Yang J, Li X, Chen X, et al. Small interfering RNA targeting IKKbeta prevents renal ischemia-reperfusion injury in rats. Am J Physiol Renal Physiol. 2011;300(4):F857-63.
99. Kumar D, Singla SK, Puri V, Puri S. The restrained expression of NF-kB in renal tissue ameliorates folic acid induced acute kidney injury in mice. PLoS One. 2015;10(1):e115947.
100. Henke N, Schmidt-Ullrich R, Dechend R, Park JK, Qadri F, Wellner M, et al. Vascular endothelial cell-specific NF-kappaB suppression attenuates hypertension-induced renal damage. Circ Res. 2007;101(3):268-76.
101. Muller DN, Dechend R, Mervaala EM, Park JK, Schmidt F, Fiebeler A, et al. NF-kappaB inhibition ameliorates angiotensin II-induced inflammatory damage in rats. Hypertension. 2000;35(1 Pt 2):193-201.
102. Lai KN. Pathogenesis of IgA nephropathy. Nat Rev Nephrol. 2012;Epub ahead of print. doi: 10.1038/nrneph.2012.58.
103. Roberts IS. Pathology of IgA nephropathy. Nat Rev Nephrol. 2014;10(8):445-54.
104. Ashizawa M, Miyazaki M, Abe K, Furusu A, Isomoto H, Harada T, et al. Detection of nuclear factor-kappaB in IgA nephropathy using Southwestern histochemistry. Am J Kidney Dis Off J Nat Kidney Found. 2003;42(1):76-86.
105. Danilewicz M, Wagrowska-Danilewicz M. Tubular NF-ΚB is overexpressed in proteinuric patients with IgA nephropathy. Folia histochemica et cytobiologica/Polish Acad Sci Polish Histochem Cytochem Soc. 2012;50(1):93-8.
106. Silva GE, Costa RS, Ravinal RC, Ramalho LZ, Dos Reis MA, Coimbra TM, et al. NF-ΚB expression in IgA nephropathy outcome. Dis Markers. 2011;31(1):9-15.
107. Lopez-Franco O, Suzuki Y, Sanjuan G, Blanco J, Hernandez-Vargas P, Yo Y, et al. Nuclear factor-kappa B inhibitors as potential novel anti-inflammatory agents for the treatment of immune glomerulonephritis. Am J Pathol. 2002;161(4):1497-505.
108. Hua KF, Yang SM, Kao TY, Chang JM, Chen HL, Tsai YJ, et al. Osthole mitigates progressive IgA nephropathy by inhibiting reactive oxygen species generation and NF-kappaB/NLRP3 pathway. PLoS One. 2013;8(10):e77794.
109. McCarthy DD, Chiu S, Gao Y, Summers-deLuca LE, Gommerman JL. BAFF induces a hyper-IgA syndrome in the intestinal lamina propria concomitant with IgA deposition in the kidney independent of LIGHT. Cell Immunol. 2006;241:85-94.
110. McCarthy DD, Kujawa J, Wilson C, Papandile A, Poreci U, Porfilio EA, et al. Mice overexpressing BAFF develop a commensal flora-dependent, IgA-associated nephropathy. J Clin Invest. 2011;121:3991-4002.
111. Mok CC, Kwok RC, Yip PS. Effect of renal disease on the standardized mortality ratio and life expectancy of patients with systemic lupus erythematosus. Arthritis Rheum. 2013;65(8):2154-60.
112. Zheng L, Sinniah R, Hsu SI. In situ glomerular expression of activated NF-kappaB in human lupus nephritis and other non-proliferative proteinuric glomerulopathy. Virchows Archiv Int J Pathol. 2006;448(2):172-83.
113. Zheng L, Sinniah R, Hsu SI. Pathogenic role of NF-kappaB activation in tubulointerstitial inflammatory lesions in human lupus nephritis. J Histochem Cytochem Off J Histochem Soc. 2008;56(5):517-29.
114. Wan X, Yang J, Xing L, Fan L, Hu B, Chen X, et al. Inhibition of IkappaB Kinase beta attenuates hypoxia-induced inflammatory mediators in rat renal tubular cells. Transpl Proc. 2011;43(5):1503-10.
115. Zhao J, Zhang H, Huang Y, Wang H, Wang S, Zhao C, et al. Bay11-7082 attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-kappaB activation. Int Immunopharmacol. 2013;17(1):116-22.
116. Bates JS, Lessard CJ, Leon JM, Nguyen T, Battiest LJ, Rodgers J, et al. Meta-analysis and imputation identifies a 109kb risk haplotype spanning TNFAIP3 associated with lupus nephritis and hematologic manifestations. Genes Immun. 2009;10(5):470-7.
117. Caster DJ, Korte EA, Nanda SK, McLeish KR, Oliver RK, G'Sell RT, et al. ABIN1 dysfunction as a genetic basis for lupus nephritis. J Am Soc Nephrol JASN. 2013;24(11):1743-54.
118. Shembade N, Harhaj EW. Regulation of NF-kappaB signaling by the A20 deubiquitinase. Cell Mol Immunol. 2012;9(2):123-30.
119. Wertz I, Dixit V. A20-a bipartite ubiquitin editing enzyme with immunoregulatory potential. Adv Exp Med Biol. 2014;809:1-12.
120. Verstrepen L, Carpentier I, Verhelst K, Beyaert R. ABINs: A20 binding inhibitors of NF-kappa B and apoptosis signaling. Biochem Pharmacol. 2009;78(2):105-14.
121. Ma A, Malynn BA. A20: linking a complex regulator of ubiquitylation to immunity and human disease. Nat Rev Immunol. 2012;12(11):774-85.
122. Nanda SK, Venigalla RK, Ordureau A, Patterson-Kane JC, Powell DW, Toth R, et al. Polyubiquitin binding to ABIN1 is required to prevent autoimmunity. J Exp Med. 2011;208(6):1215-28.
123. Jiang T, Tian F, Zheng H, Whitman SA, Lin Y, Zhang Z, et al. Nrf2 suppresses lupus nephritis through inhibition of oxidative injury and the NF-kappaB-mediated inflammatory response. Kidney Int. 2014;85(2):333-43.
124. Hayes JD, Dinkova-Kostova AT. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci. 2014;39(4):199-218.
125. Li W, Khor TO, Xu C, Shen G, Jeong WS, Yu S, et al. Activation of Nrf2-antioxidant signaling attenuates NFkappaB-inflammatory response and elicits apoptosis. Biochem Pharmacol. 2008;76(11):1485-9.
126. Yoh K, Itoh K, Enomoto A, Hirayama A, Yamaguchi N, Kobayashi M, et al. Nrf2-deficient female mice develop lupus-like autoimmune nephritis. Kidney Int. 2001;60(4):1343-53.
127. Winkles JA. The TWEAK-Fn14 cytokine-receptor axis: discovery, biology and therapeutic targeting. Nat Rev Drug Discov. 2008;7(5):411-25.
128. Poveda J, Tabara LC, Fernandez-Fernandez B, Martin-Cleary C, Sanz AB, Selgas R, et al. TWEAK/Fn14 and non-canonical NF-kappaB signaling in kidney disease. Front Immunol. 2013;4:447.
129. Sanz AB, Sanchez-Nino MD, Ortiz A. TWEAK, a multifunctional cytokine in kidney injury. Kidney Int. 2011;80(7):708-18.
130. Justo P, Sanz AB, Sanchez-Nino MD, Winkles JA, Lorz C, Egido J, et al. Cytokine cooperation in renal tubular cell injury: the role of TWEAK. Kidney Int. 2006;70(10):1750-8.
131. Sanz AB, Izquierdo MC, Sanchez-Nino MD, Ucero AC, Egido J, Ruiz-Ortega M, et al. TWEAK and the progression of renal disease: clinical translation. Nephrol Dial Transpl Off Publ Eur Dial Transpl Assoc Eur Renal Assoc. 2014;29(Suppl 1):i54-62.
132. Sasaki Y, Shimizu Y, Suzuki Y, Horikoshi S, Tomino Y. TWEAK/Fn14 system and crescent formation in IgA nephropathy. BMC Nephrol. 2015;16:27.
133. Sanz AB, Justo P, Sanchez-Nino MD, Blanco-Colio LM, Winkles JA, Kreztler M, et al. The cytokine TWEAK modulates renal tubulointerstitial inflammation. J Am Soc Nephrol JASN. 2008;19(4):695-703.
134. Sanz AB, Sanchez-Nino MD, Izquierdo MC, Jakubowski A, Justo P, Blanco-Colio LM, et al. TWEAK activates the non-canonical NFkappaB pathway in murine renal tubular cells: modulation of CCL21. PLoS One. 2010;5(1):e8955.
135. Ucero AC, Benito-Martin A, Fuentes-Calvo I, Santamaria B, Blanco J, Lopez-Novoa JM, et al. TNF-related weak inducer of apoptosis (TWEAK) promotes kidney fibrosis and Ras-dependent proliferation of cultured renal fibroblast. Biochim Biophys Acta. 2013;1832(10):1744-55.
136. Zhao Z, Burkly LC, Campbell S, Schwartz N, Molano A, Choudhury A, et al. TWEAK/Fn14 interactions are instrumental in the pathogenesis of nephritis in the chronic graft-versus-host model of systemic lupus erythematosus. J Immunol. 2007;179(11):7949-58.
137. Xia Y, Campbell SR, Broder A, Herlitz L, Abadi M, Wu P, et al. Inhibition of the TWEAK/Fn14 pathway attenuates renal disease in nephrotoxic serum nephritis. Clin Immunol. 2012;145(2):108-21.
138. Xia Y, Herlitz LC, Gindea S, Wen J, Pawar RD, Misharin A, et al. Deficiency of fibroblast growth factor-inducible 14 (Fn14) preserves the filtration barrier and ameliorates lupus nephritis. J Am Soc Nephrol JASN. 2015;26(5):1053-70.
139. Sun SC, Chang JH, Jin J. Regulation of nuclear factor-kappaB in autoimmunity. Trends Immunol. 2013;34(6):282-9.
140. Ooi JD, Kitching AR, Holdsworth SR. Review: T helper 17 cells: their role in glomerulonephritis. Nephrology. 2010;15(5):513-21.
141. Turner JE, Paust HJ, Steinmetz OM, Panzer U. The Th17 immune response in renal inflammation. Kidney Int. 2010;77(12):1070-5.
142. Dong X, Bachman LA, Miller MN, Nath KA, Griffin MD. Dendritic cells facilitate accumulation of IL-17 T cells in the kidney following acute renal obstruction. Kidney Int. 2008;74(10):1294-309.
143. Summers SA, Steinmetz OM, Li M, Kausman JY, Semple T, Edgtton KL, et al. Th1 and Th17 cells induce proliferative glomerulonephritis. J Am Soc Nephrol JASN. 2009;20(12):2518-24.
144. Ooi JD, Phoon RK, Holdsworth SR, Kitching AR. IL-23, not IL-12, directs autoimmunity to the Goodpasture antigen. J Am Soc Nephrol JASN. 2009;20(5):980-9.
145. Paust HJ, Turner JE, Steinmetz OM, Peters A, Heymann F, Holscher C, et al. The IL-23/Th17 axis contributes to renal injury in experimental glomerulonephritis. J Am Soc Nephrol JASN. 2009;20(5):969-79.
146. Gan PY, Steinmetz OM, Tan DS, O'Sullivan KM, Ooi JD, Iwakura Y, et al. Th17 cells promote autoimmune anti-myeloperoxidase glomerulonephritis. J Am Soc Nephrol JASN. 2010;21(6):925-31.
147. Chan OT, Madaio MP, Shlomchik MJ. The central and multiple roles of B cells in lupus pathogenesis. Immunol Rev. 1999;169:107-21.
148. Gregersen JW, Jayne DR. B cell depletion in the treatment of lupus nephritis. Nat Rev Nephrol. 2012;8(9):505-14.
149. Kaileh M, Sen R. NF-kappaB function in B lymphocytes. Immunol Rev. 2012;246(1):254-71.
150. Mackay F, Browning JL. BAFF: a fundamental survival factor for B cells. Nat Rev Immunol. 2002;2(7):465-75.
151. Li W, Peng X, Liu Y, Liu H, Liu F, He L, et al. TLR9 and BAFF: their expression in patients with IgA nephropathy. Mol Med Rep. 2014;10(3):1469-74.
152. Frieri M, Heuser W, Bliss J. Efficacy of novel monoclonal antibody belimumab in the treatment of lupus nephritis. J Pharmacol Pharmacother. 2015;6(2):71-6.
153. Neusser MA, Lindenmeyer MT, Edenhofer I, Gaiser S, Kretzler M, Regele H, et al. Intrarenal production of B cell survival factors in human lupus nephritis. Modern Pathol Off J United StatesCan Acad Pathol Inc. 2011;24(1):98-107.
154. Vincent FB, Northcott M, Hoi A, Mackay F, Morand EF. Association of serum B cell activating factor from the tumour necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) with central nervous system and renal disease in systemic lupus erythematosus. Lupus. 2013;22(9):873-84.
155. Xin G, Shi W, Xu LX, Su Y, Yan LJ, Li KS. Serum BAFF is elevated in patients with IgA nephropathy and associated with clinical and histopathological features. J Nephrol. 2013;26(4):683-90.