Regulation of tissue homeostasis by NF-B signalling: Implications for inflammatory diseases

Nature Reviews Immunology

Volumn 9, Issue 11, 2009, Pages 778-788

  Pasparakis, Manolis ^a  

^a UNIVERSITY OF COLOGNE   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN;

HOMEOSTASIS; IMMUNOCOMPETENT CELL; INFLAMMATORY DISEASE; KERATINOCYTE; LIVER CELL; PRIORITY JOURNAL; REVIEW; SKIN EPITHELIUM;

ANIMALS; EPIDERMIS; EPITHELIAL CELLS; HEPATOCYTES; HOMEOSTASIS; HUMANS; INFLAMMATION; INTESTINES; KERATINOCYTES; LIVER; MICE; NF-KAPPA B; SIGNAL TRANSDUCTION; SKIN;

EID: 70350513270     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri2655     Document Type: Review

References (120)

1. Vallabhapurapu, S. & Karin, M. Regulation and function of NF-KB transcription factors in the immune system. Annu. Rev. Immunol. 27, 693-733 (2009).
2. Ghosh, S. & Hayden, M. S. New regulators of NF-KB in inflammation. Nature Rev. Immunol. 8, 837-848 (2008).
3. Woronicz, J. D., Gao, X., Cao, Z., Rothe, M. & Goeddel, D. V. IKB kinase-(3: NF-KB activation and complex formation with IKB kinase-a and NIK. Science 278, 866-869 (1997).
4. Mercurio, F et al. IKK-1 and IKK-2: cytokine-activated IKB kinases essential for NF-KB activation. Science 278, 860-866 (1997).
5. Zandi, E., Rothwarf, D. M., Delhase, M., Hayakawa, M. & Karin, M. The IKB kinase complex (IKK) contains two kinase subunits, IKKa and IKK(3, necessary for IKB phosphorylation and NF-KB activation. Cell 91, 243-252 (1997).
6. DiDonato, J. A., Hayakawa, M., Rothwarf, D. M., Zandi, E. & Karin, M. A cytokine-responsive IKB kinase that activates the transcription factor NF-KB. Nature 388, 548-554 (1997).
7. Yamaoka, S. et al. Complementation cloning of NEMO, a component of the IKB kinase complex essential for NF-KB activation. Cell 93, 1231-1240 (1998).
8. Rothwarf, D. M., Zandi, E., Natoli, G. & Karin, M. IKK-y is an essential regulatory subunit of the IKB kinase complex. Nature 395, 297-300 (1998).
9. Senftleben, U. et al. Activation by IKKa of a second, evolutionary conserved, NF-KB signaling pathway. Science 293, 1495-1499 (2001).
10. Derudder, E. et al. RelB/p50 dimers are differentially regulated by tumor necrosis factor-a and lymphotoxin-p receptor activation: critical roles for p100. J. Biol. Chem. 278, 23278-23284 (2003).
11. Muller, J. R. & Siebenlist, U. Lymphotoxin-p receptor induces sequential activation of distinct NF-KB factors via separate signaling pathways. J. Biol. Chem. 278, 12006-12012 (2003).
12. Makris, C. et al. Female mice heterozygous for IKKy/ NEMO deficiencies develop a dermatopathy similar to the human X-linked disorder incontinentia pigmenti. Mol. Cell 5, 969-979 (2000).
13. Rudolph, D. et al. Severe liver degeneration and lack of NF-KB activation in NEMO/IKKy-deficient mice. Genes Dev 14, 854-862 (2000).
14. Schmidt-Supprian, M. et al. NEMO/IKKy-deficient mice model incontinentia pigmenti. Mol. Cell 5, 981-992 (2000).
15. Li, Q., Van Antwerp, D., Mercurio, F, Lee, K. F & Verma, I. M. Severe liver degeneration in mice lacking the IKB kinase 2 gene. Science 284, 321-325 (1999).
16. Li, Z. W. et al. The IKK(3 subunit of IKB kinase (IKK) is essential for nuclear factor KB activation and prevention of apoptosis. J. Exp. Med. 189, 1839-1845 (1999).
17. Tanaka, M. et al. Embryonic lethality, liver degeneration, and impaired NF-KB activation in IKK-p-deficient mice. Immunity 10, 421-429 (1999).
18. Li, Q., Estepa, G., Memet, S., Israel, A. & Verma, I. M. Complete lack of NF-KB activity in IKK1 and IKK2 double-deficient mice: additional defect in neurulation. Genes Dev. 14, 1729-1733 (2000).
19. Luedde, T et al. IKK1 and IKK2 cooperate to maintain bile duct integrity in the liver. Proc. Natl Acad. Sci. USA 105, 9733-9738 (2008).
20. Lenardo, M. J. & Baltimore, D. NF-KB: a pleiotropic mediator of inducible and tissue-specific gene control. Cell 58, 227-229 (1989).
21. Ghosh, S., May, M. J. & Kopp, E. B. NF-KB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 16, 225-260 (1998).
22. Liu, Z. G., Hsu, H., Goeddel, D. V & Karin, M. Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-KB activation prevents cell death. Cell 87, 565-576 (1996).
23. Van Antwerp, D. J., Martin, S. J., Kafri, T, Green, D. R. & Verma, I. M. Suppression of TNF-a-induced apoptosis by NF-KB. Science 274, 787-789 (1996).
24. Wang, C. Y., Mayo, M. W. & Baldwin, A. S., Jr. TNF-and cancer therapy-induced apoptosis: potentiation by inhibition of NF-KB. Science 274, 784-787 (1996).
25. Tsukahara, T et al. Induction of Bcl-xL expression by human T-cell leukemia virus type 1 Tax through NF-KB in apoptosis-resistant T-cell transfectants with Tax. J. Virol. 73, 7981-7987 (1999). (Pubitemid 29441656)
26. Kreuz, S., Siegmund, D., Scheurich, P. & Wajant, H. NF-KB inducers upregulate cFLIP, a cycloheximide-sensitive inhibitor of death receptor signaling. Mol. Cell Biol. 21, 3964-3973 (2001).
27. Micheau, O., Lens, S., Gaide, O., Alevizopoulos, K. & Tschopp, J. NF-KB signals induce the expression of c-FLIP. Mol. Cell Biol. 21, 5299-5305 (2001).
28. Wang, C. Y, Mayo, M. W, Korneluk, R. G., Goeddel, D. V & Baldwin, A. S., Jr. NF-KB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP 1 and c-IAP2 to suppress caspase-8 activation. Science 281, 1680-1683 (1998).
29. Stehlik, C. et al. Nuclear factor (NF)-KB-regulated X-chromosome-linked iap gene expression protects endothelial cells from tumor necrosis factor a-induced apoptosis. J. Exp. Med. 188, 211-216 (1998).
30. Sakon, S. et al. NF-KB inhibits TNF-induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death. EMBO J. 22, 3898-3909 (2003).
31. Pham, C. G. et al. Ferritin heavy chain upregulation by NF-KB inhibits TNFa-induced apoptosis by suppressing reactive oxygen species. Cell 119, 529-542 (2004).
32. Pasparakis, M., Luedde, T & Schmidt-Supprian, M. Dissection of the NF-KB signalling cascade in transgenic and knockout mice. Cell Death Differ. 13, 861-872 (2006).
33. Beg, A. A., Sha, W C, Bronson, R. T, Ghosh, S. & Baltimore, D. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-KB. Nature 376, 167-170 (1995).
34. Beg, A. A., Sha, W C, Bronson, R. T & Baltimore, D. Constitutive NF-KB activation, enhanced granulopoiesis, and neonatal lethality in IKBCI-deficient mice. Genes Dev. 9, 2736-2746 (1995).
35. Klement, J. F et al. IKBCI deficiency results in a sustained NF-KB response and severe widespread dermatitis in mice. Mol. Cell Biol. 16, 2341-2349 (1996).
36. Lee, E. G. et al. Failure to regulate TNF-induced NF-KB and cell death responses in A20-deficient mice. Science 289, 2350-2354 (2000).
37. Rebholz, B. et al. Crosstalk between keratinocytes and adaptive immune cells in an IKBCI protein-mediated inflammatory disease of the skin. Immunity 27, 296-307 (2007).
38. Cai, D. et al. IKK(3/NF-KB activation causes severe muscle wasting in mice. Cell 119, 285-298 (2004).
39. Greten, F R. et al. IKK(3 links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118, 285-296 (2004).
40. Broide, D. H. et al. Allergen-induced peribronchial fibrosis and mucus production mediated by IKB kinase (3-dependent genes in airway epithelium. Proc. Natl Acad. Sci. USA 102, 17723-17728 (2005).
41. Acharyya, S. et al. Interplay of IKK/NF-KB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy. J. Clin. Invest. 117, 889-901 (2007).
42. Arkan, M. C. et al. IKK-(3 links inflammation to obesity-induced insulin resistance. Nature Med. 11, 191-198 (2005).
43. Cai, D. et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-(3 and NF-KB. Nature Med. 11, 183-190 (2005).
44. Tschachler, E. Psoriasis: the epidermal component. Clin. Dermatol. 25, 589-595 (2007).
45. Pasparakis, M. et al. TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2. Nature 417, 861-866 (2002).
46. Stratis, A. et al. Pathogenic role for skin macrophages in a mouse model of keratinocyte-induced psoriasislike skin inflammation. J. Clin. Invest. 116, 2094-2 104 (2006).
47. Sato, S. et al. Essential function for the kinase TAK1 in innate and adaptive immune responses. Nature Immunol. 6, 1087-1095 (2005).
48. Wang, C. et al. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412, 346-351 (2001).
49. Ninomiya-Tsuji, J. et al. The kinase TAK1 can activate the NIK-IKB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 398, 252-256 (1999).
50. Omori, E. et al. TAK1 is a master regulator of epidermal homeostasis involving skin inflammation and apoptosis. J. Biol. Chem. 281, 19610-19617 (2006).
51. Omori, E., Morioka, S., Matsumoto, K. & Ninomiya-Tsuji, J. TAK1 regulates reactive oxygen species and cell death in keratinocytes, which is essential for skin integrity. J. Biol. Chem. 283, 26161-26168 (2008).
52. van Hogerlinden, M., Rozell, B. L., Ahrlund-Richter, L. & Toftgard, R. Squamous cell carcinomas and increased apoptosis in skin with inhibited Rel/nuclear factor-κB signaling. Cancer Res. 59, 3299-3303 (1999).
53. Lind, M. H. et al. Tumor necrosis factor receptor 1-mediated signaling is required for skin cancer development induced by NF-κB inhibition. Proc. Natl Acad. Sci. USA 101, 4972-4977 (2004).
54. Seitz, C. S., Lin, Q., Deng, H. & Khavari, P. A. Alterations in NF-κB function in transgenic epithelial tissue demonstrate a growth inhibitory role for NF-κB. Proc. Natl Acad. Sci. USA 95, 2307-2312 (1998).
55. Gugasyan, R. et al. The transcription factors c-rel and RelA control epidermal development and homeostasis in embryonic and adult skin via distinct mechanisms. Mol. Cell Biol. 24, 5733-5745 (2004).
56. Smahi, A. et al. Genomic rearrangement in NEMO impairs NF-κB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature 405, 466-472 (2000).
57. Berlin, A. L., Paller, A. S. & Chan, L. S. Incontinentia pigmenti: a review and update on the molecular basis of pathophysiology. J. Am. Acad. Dermatol. 47, 169-187 (2002).
58. Nenci, A. et al. Skin lesion development in a mouse model of incontinentia pigmenti is triggered by NEMO deficiency in epidermal keratinocytes and requires TNF signaling. Hum. Mol. Genet. 15, 531-542 (2006).
59. Stratis, A. et al. Localized inflammatory skin disease following inducible ablation of IκB kinase 2 in murine epidermis. J. Invest. Dermatol. 126, 614-620 (2006).
60. Ulvmar, M. H., Sur, I., Memet, S. & Toftgard, R. Timed NF-κB inhibition in skin reveals dual independent effects on development of HED/EDA and chronic inflammation. J. Invest. Dermatol. 11 Jun 2009 (doi:10.1038/jid. 2009.126).
61. Sur, I., Ulvmar, M. & Toftgard, R. The two-faced NF-κB in the skin. Int. R e v. Immunol. 27, 205-223 (2008).
62. Boutin, A. T. et al. Epidermal sensing of oxygen is essential for systemic hypoxic response. Cell 133, 223-234 (2008).
63. Kamata, H. et al. Reactive oxygen species promote TNFα-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 120, 649-661 (2005).
64. Rius, J. et al. NF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α. Nature 453, 807-811 (2008).
65. Szabowski, A. et al. c-Jun and JunB antagonistically control cytokine-regulated mesenchymal-epidermal interaction in skin. Cell 103, 745-755 (2000).
66. Chaudhari, U. et al. Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial. Lancet 357, 1842-1847 (2001).
67. Mossner, R., Schon, M. P. & Reich, K. Tumor necrosis factor antagonists in the therapy of psoriasis. Clin. Dermatol. 26, 486-502 (2008).
68. Strober, W., Fuss, I. & Mannon, P. The fundamental basis of inflammatory bowel disease. J. Clin. Invest. 11 7 , 514-521 (2007).
69. Ellis, R. D. et al. Activation of nuclear factor κB in Crohn's disease. Inflamm. Res. 47, 440-445 (1998).
70. Schreiber, S., Nikolaus, S. & Hampe, J. Activation of nuclear factor κB in inflammatory bowel disease. Gut 42, 477-484 (1998). Neurath, M. F., Pettersson, S.
71. Meyer zum Buschenfelde, K. H. & Strober, W. Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-κB abrogates established experimental colitis in mice. Nature Med. 2, 998-1004 (1996).
72. Dave, S. H. et al. Amelioration of chronic murine colitis by peptide-mediated transduction of the IκB kinase inhibitor NEMO binding domain peptide. J. Immunol. 179, 7852-7859 (2007).
73. Shibata, W. et al. Cutting edge: The IκB kinase (IKK) inhibitor, NEMO-binding domain peptide, blocks inflammatory injury in murine colitis. J. Immunol. 179, 2681-2685 (2007).
74. Nenci, A. et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446, 557-561 (2007).
75. Wehkamp, J., Fellermann, K., Herrlinger, K. R., Bevins, C. L. & Stange, E. F. Mechanisms of disease: defensins in gastrointestinal diseases. Nature Clin. Pract. Gastroenterol. Hepatol. 2, 406-415 (2005).
76. Fellermann, K. et al. A chromosome 8 gene-cluster polymorphism with low human β-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am. J. Hum. Genet. 79, 439-448 (2006).
77. Fish, J. D., Duerst, R. E., Gelfand, E. W., Orange, J. S. & Bunin, N. Challenges in the use of allogeneic hematopoietic SCT for ectodermal dysplasia with immune deficiency. Bone Marrow Transplant. 43, 217-221 (2009).
78. Pai, S. Y. et al. Allogeneic transplantation successfully corrects immune defects, but not susceptibility to colitis, in a patient with nuclear factor-κB essential modulator deficiency. J. Allergy Clin. Immunol. 122, 1113-1118 e1 (2008).
79. Kawai, T. & Akira, S. Signaling to NF-κB by Toll-like receptors. Trends Mol. Med. 13, 460-469 (2007).
80. Kawai, T. , Adachi, O., Ogawa, T., Takeda, K. & Akira, S. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11 , 115-122 (1999).
81. Adachi, O. et al. Targeted disruption of the MyD88 gene results in loss of IL-1-and IL-18-mediated function. Immunity 9, 143-150 (1998).
82. Vijay-Kumar, M. et al. Deletion of TLR5 results in spontaneous colitis in mice. J. Clin. Invest. 117, 3909-3921 (2007).
83. Lee, J. et al. Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nature Cell Biol. 8, 1327-1336 (2006).
84. Rakoff-Nahoum, S., Hao, L. & Medzhitov, R. Role of Toll-like receptors in spontaneous commensal-dependent colitis. Immunity 25, 319-329 (2006).
85. Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S. & Medzhitov, R. Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 11 8 , 229-241 (2004).
86. Araki, A. et al. MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis. J. Gastroenterol. 40, 16-23 (2005).
87. Cario, E., Gerken, G. & Podolsky, D. K. Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function. Gastroenterology 132, 1359-1374 (2007).
88. Cario, E. & Podolsky, D. K. Intestinal epithelial TOLLerance versus inTOLLerance of commensals. Mol. Immunol. 42, 887-893 (2005).
89. Leaphart, C. L. et al. A critical role for TLR4 in the pathogenesis of necrotizing enterocolitis by modulating intestinal injury and repair. J. Immunol. 179, 4808-4820 (2007).
90. Sandborn, W. J. & Hanauer, S. B. Antitumor necrosis factor therapy for inflammatory bowel disease: a review of agents, pharmacology, clinical results, and safety. Inflamm. Bowel Dis. 5, 119-133 (1999).
91. Atreya, R. & Neurath, M. F. New therapeutic strategies for treatment of inflammatory bowel disease. Mucosal Immunol. 1, 175-182 (2008).
92. Armaka, M. et al. Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases. J. Exp. Med. 205, 331-337 (2008).
93. Kajino-Sakamoto, R. et al. Enterocyte-derived TAK1 signaling prevents epithelium apoptosis and the development of ileitis and colitis. J. Immunol. 181, 1143-1152 (2008).
94. Kim, J. Y, Kajino-Sakamoto, R., Omori, E., Jobin, C. & Ninomiya-Tsuji, J. Intestinal epithelial-derived TAK1 signaling is essential for cytoprotection against chemical-induced colitis. PLoS ONE 4, e4561 (2009).
95. Frank, D. N. & Pace, N. R. Gastrointestinal microbiology enters the metagenomics era. Curr. Opin. Gastroenterol. 24, 4-10 (2008).
96. Eckburg, P. B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635-1638 (2005).
97. Manson, J. M., Rauch, M. & Gilmore, M. S. The commensal microbiology of the gastrointestinal tract. Adv. Exp. Med. Biol. 635, 15-28 (2008).
98. Steinbrecher, K. A., Harmel-Laws, E., Sitcheran, R. & Baldwin, A. S. Loss of epithelial RelA results in deregulated intestinal proliferative/ apoptotic homeostasis and susceptibility to inflammation. J. Immunol. 180, 2588-2599 (2008).
99. Eckmann, L. et al. Opposing functions of IKKp during acute and chronic intestinal inflammation. Proc. Natl Acad. Sci. USA 105, 15058-15063 (2008).
100. Egan, L. J. et al. IicB-kinasep-dependent NF-KB activation provides radioprotection to the intestinal epithelium. Proc. Natl Acad. Sci. USA 101, 2452-2457 (2004).
101. Chen, L. W. et al. The two faces of IKK and NF-KB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion. Nature Med. 9, 575-581 (2003).
102. Zaph, C. et al. Epithelial-cell-intrinsic IKK-p expression regulates intestinal immune homeostasis. Nature 446, 552-556 (2007).
103. Lee, H. C. & Ziegler, S. F Inducible expression of the proallergic cytokine thymic stromal lymphopoietin in airway epithelial cells is controlled by NFKB. Proc. Natl Acad. Sci. USA 104, 914-919 (2007).
104. Liu, Y. J. et al. TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation. Annu. Rev. Immunol. 25, 193-2 19 (2007).
105. Doi, T. S. et al. Absence of tumor necrosis factor rescues RelA-deficient mice from embryonic lethality. Proc. Natl Acad. Sci. USA 96, 2994-2999 (1999).
106. Alcamo, E. et al. Targeted mutation of TNF receptor I rescues the RelA-deficient mouse and reveals a critical role for NF-KB in leukocyte recruitment. J. Immunol. 167, 1592-1600 (2001).
107. Luedde, T et al. Deletion of NEMO/IKKy in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma. Cancer Cell 11, 119-132 (2007).
108. Maeda, S. et al. IKKp is required for prevention of apoptosis mediated by cell-bound but not by circulating TNFa. Immunity 19, 725-737 (2003).
109. Luedde, T. et al. Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury. J. Clin. Invest. 115, 849-859 (2005).
110. Geisler, F, Algül, H., Paxian, S. & Schmid, R. M. Genetic inactivation of RelA/p65 sensitizes adult mouse hepatocytes to TNF-induced apoptosis in vivo and in vitro. Gastroenterology 132, 2489-2503 (2007).
111. Chaisson, M. L, Brooling, J. T, Ladiges, W., Tsai, S. & Fausto, N. Hepatocyte-specific inhibition of NF-KB leads to apoptosis after TNF treatment, but not after partial hepatectomy. J. Clin. Invest. 110, 193-202 (2002).
112. Wilson, N. S., Dixit, V. & Ashkenazi, A. Death receptor signal transducers: nodes of coordination in immune signaling networks. Nature Immunol. 10, 348-355 (2009).
113. Lavon, I. et al. High susceptibility to bacterial infection, but no liver dysfunction, in mice compromised for hepatocyte NF-KB activation. Nature Med. 6, 573-577 (2000).
114. Maeda, S., Kamata, H., Luo, J. L, Leffert, H. & Karin, M. IKKp couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 121, 977-990 (2005).
115. Herrmann, O. et al. IKK mediates ischemia-induced neuronal death. Nature Med. 11, 1322-1329 (2005).
116. van Loo, G. et al. Inhibition of transcription factor NF-KB in the central nervous system ameliorates autoimmune encephalomyelitis in mice. Nature Immunol. 7, 954-961 (2006).
117. Mourkioti, F et al. Targeted ablation of IKK2 improves skeletal muscle strength, maintains mass, and promotes regeneration. J. Clin. Invest. 116, 2945-2954 (2006).
118. Rohl, M. et al. Conditional disruption of IKB kinase 2 fails to prevent obesity-induced insulin resistance. J. Clin. Invest. 113, 474-481 (2004).
119. Baumann, B. et al. Constitutive IKK2 activation in acinar cells is sufficient to induce pancreatitis in vivo. J. Clin. Invest. 117, 1502-1513 (2007).
120. Norlin, S., Ahlgren, U. & Edlund, H. Nuclear factor-KB activity in p-cells is required for glucose-stimulated insulin secretion. Diabetes 54, 125-132 (2005).