NF-κB as a target for modulating inflammatory responses

Current Pharmaceutical Design

Volumn 18, Issue 35, 2012, Pages 5735-5745

  Gasparini, Chiara ^a   Feldmann, Marc ^b  

^a INSTITUTE FOR MATERNAL AND CHILD HEALTH IRCCS BURLO GAROFOLO   (Italy)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Anti inflammatory; Cytokines; Dendritic cells; Inflammation; NF B; Primary cells; Small molecules nucleic acids; Small molecules peptides

Indexed keywords

ACETYLSALICYLIC ACID; ARACHIDONIC ACID; BORTEZOMIB; CELECOXIB; I KAPPA B ALPHA; I KAPPA B KINASE; IBUPROFEN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDOMETACIN; NONSTEROID ANTIINFLAMMATORY AGENT; PROTEASOME; PROTEIN P50; PROTEIN P52; SALAZOSULFAPYRIDINE; STAT1 PROTEIN;

APOPTOSIS; DENDRITIC CELL; ENDOTHELIUM CELL; ENTERITIS; ENZYME ACTIVATION; FIBROBLAST; GENE EXPRESSION; HUMAN; IMMUNE RESPONSE; IMMUNOMODULATION; IMMUNOTHERAPY; IN VITRO STUDY; INFLAMMATION; MACROPHAGE; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION;

ACUTE DISEASE; ANIMALS; CHRONIC DISEASE; DENDRITIC CELLS; GENE EXPRESSION REGULATION; HUMANS; IMMUNOTHERAPY; INFLAMMATION; NF-KAPPA B; SIGNAL TRANSDUCTION;

EID: 84870199424     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161212803530763     Document Type: Review

References (110)

1. Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell 2010; 140: 771-6.
2. McCall CE, El Gazzar M, Liu T, Vachharajani V, Yoza B. Epigenetics, bioenergetics, and microRNA coordinate genespecific reprogramming during acute systemic inflammation. J Leukoc Biol 2011; 90: 439-46.
3. Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 2011; 34: 637-50.
4. Rao P, Knaus EE. Evolution of nonsteroidal anti-inflammatory drugs (NSAIDs): cyclooxygenase (COX) inhibition and beyond. J Pharm Pharm Sci 2008; 11: 81s-110s.
5. Kopp E, Ghosh S. Inhibition of NF-kappa B by sodium salicylate and aspirin. Science 1994; 265: 956-9.
6. Yin MJ, Yamamoto Y, Gaynor RB. The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature 1998; 396: 77-80.
7. Gessi S, Merighi S, Borea PA. Glucocorticoid's pharmacology: past, present and future. Curr Pharm Des 2010; 16: 3540-53.
8. Auphan N, DiDonato JA, Rosette C, Helmberg A, Karin M. Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science 1995; 270: 286-90.
9. De Bosscher K, Vanden Berghe W, Haegeman G. Cross-talk between nuclear receptors and nuclear factor kappaB. Oncogene 2006; 25: 6868-86.
10. Neumann M, Naumann M. Beyond IkappaBs: alternative regulation of NF-kappaB activity. FASEB J 2007; 21: 2642-54.
11. Abraham SM, Lawrence T, Kleiman A, et al. Antiinflammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatase 1. J Exp Med 2006; 203: 1883-9.
12. Feldmann M, Steinman L. Design of effective immunotherapy for human autoimmunity. Nature 2005; 435: 612-9.
13. Williams RO, Paleolog E, Feldmann M. Cytokine inhibitors in rheumatoid arthritis and other autoimmune diseases. Curr Opin Pharmacol 2007; 7: 412-7.
14. Feldmann M, Brennan FM, Williams RO, Woody JN, Maini RN. The transfer of a laboratory based hypothesis to a clinically useful therapy: the development of anti-TNF therapy of rheumatoid arthritis. Best Pract Res Clin Rheumatol 2004; 18: 59-80.
15. Feldmann M. Development of anti-TNF therapy for rheumatoid arthritis. Nat Rev Immunol 2002; 2: 364-71.
16. Lublin F. History of modern multiple sclerosis therapy. J Neurol 2005; 252 Suppl 3: iii3-iii9.
17. O'Sullivan BJ, Pai S, Street S, et al. Immunotherapy with costimulatory dendritic cells to control autoimmune inflammation. J Immunol 2011; 187: 4018-30.
18. Djouad F, Bouffi C, Ghannam S, Noel D, Jorgensen C. Mesenchymal stem cells: innovative therapeutic tools for rheumatic diseases. Nat Rev Rheumatol 2009; 5: 392-9.
19. Sakaguchi S, Powrie F, Ransohoff RM. Re-establishing immunological self-tolerance in autoimmune disease. Nat Med 2012; 18: 54-8.
20. Foxwell B, Browne K, Bondeson J, et al. Efficient adenoviral infection with IkappaB alpha reveals that macrophage tumor necrosis factor alpha production in rheumatoid arthritis is NFkappaB dependent. Proc Natl Acad Sci USA 1998; 95: 8211-5.
21. Lawrence T, Fong C. The resolution of inflammation: antiinflammatory roles for NF-kappaB. Int J Biochem Cell Biol 2010; 42: 519-23.
22. Lawrence T, Gilroy DW, Colville-Nash PR, Willoughby DA. Possible new role for NF-kappaB in the resolution of inflammation. Nat Med 2001; 7: 1291-7.
23. Sen R, Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell 1986; 47: 921-8.
24. Smale ST. Hierarchies of NF-kappaB target-gene regulation. Nat Immunol 2011; 12: 689-94.
25. Oeckinghaus A, Hayden MS, Ghosh S. Crosstalk in NF-kappaB signaling pathways. Nat Immunol 2011; 12: 695-708.
26. Ruland J. Return to homeostasis: downregulation of NF-kappaB responses. Nat Immunol 2011; 12: 709-14.
27. Ben-Neriah Y, Karin M. Inflammation meets cancer, with NFkappaB as the matchmaker. Nat Immunol 2011; 12: 715-23.
28. Ghosh S, Hayden MS. Celebrating 25 years of NF-kappaB research. Immunol Rev 2012; 246: 5-13.
29. Ghosh G, Wang VY, Huang DB, Fusco A. NF-kappaB regulation: lessons from structures. Immunol Rev 2012; 246: 36-58.
30. Hinz M, Arslan SC, Scheidereit C. It takes two to tango: IkappaBs, the multifunctional partners of NF-kappaB. Immunol Rev 2012; 246: 59-76.
31. Sun SC. The noncanonical NF-kappaB pathway. Immunol Rev 2012; 246: 125-40.
32. Natoli G. NF-kappaB and chromatin: ten years on the path from basic mechanisms to candidate drugs. Immunol Rev 2012; 246: 183-92.
33. Boldin MP, Baltimore D. MicroRNAs, new effectors and regulators of NF-kappaB. Immunol Rev 2012; 246: 205-20.
34. DiDonato JA, Mercurio F, Karin M. NF-kappaB and the link between inflammation and cancer. Immunol Rev 2012; 246: 379-400.
35. Baldwin AS. Regulation of cell death and autophagy by IKK and NF-kappaB: critical mechanisms in immune function and cancer. Immunol Rev 2012; 246: 327-45.
36. Ghosh S, May MJ, Kopp EB. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol 1998; 16: 225-60.
37. Huang DB, Vu D, Ghosh G. NF-kappaB RelB forms an intertwined homodimer. Structure 2005; 13: 1365-73.
38. Senftleben U, Cao Y, Xiao G, et al. Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science 2001; 293: 1495-9.
39. Derudder E, Dejardin E, Pritchard LL, et al. RelB/p50 dimers are differentially regulated by tumor necrosis factor-alpha and lymphotoxin-beta receptor activation: critical roles for p100. J Biol Chem 2003; 278: 23278-84.
40. Dejardin E, Droin NM, Delhase M, et al. The lymphotoxin-beta receptor induces different patterns of gene expression via two NFkappaB pathways. Immunity 2002; 17: 525-35.
41. Bonizzi G, Karin M. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 2004; 25: 280-8.
42. Hoffmann A, Baltimore D. Circuitry of nuclear factor kappaB signaling. Immunol Rev 2006; 210: 171-86.
43. Natoli G. Maintaining cell identity through global control of genomic organization. Immunity 2010; 33: 12-24.
44. Ghisletti S, Barozzi I, Mietton F, et al. Identification and characterization of enhancers controlling the inflammatory gene expression program in macrophages. Immunity 2010; 32: 317-28.
45. Simmonds RE, Foxwell BM. Signalling, inflammation and arthritis: NF-kappaB and its relevance to arthritis and inflammation. Rheumatology (Oxford) 2008; 47: 584-90.
46. Smith C, Andreakos E, Crawley JB, et al. NF-kappaB-inducing kinase is dispensable for activation of NF-kappaB in inflammatory settings but essential for lymphotoxin beta receptor activation of NF-kappaB in primary human fibroblasts. J Immunol 2001; 167: 5895-903.
47. Andreakos E, Smith C, Kiriakidis S, et al. Heterogeneous requirement of IkappaB kinase 2 for inflammatory cytokine and matrix metalloproteinase production in rheumatoid arthritis: implications for therapy. Arthritis Rheum 2003; 48: 1901-12.
48. Conron M, Andreakos E, Pantelidis P, et al. Nuclear factor-kappaB activation in alveolar macrophages requires IkappaB kinase-beta, but not nuclear factor-kappaB inducing kinase. Am J Respir Crit Care Med 2002; 165: 996-1004.
49. Andreakos E, Smith C, Monaco C, et al. Ikappa B kinase 2 but not NF-kappa B-inducing kinase is essential for effective DC antigen presentation in the allogeneic mixed lymphocyte reaction. Blood 2003; 101: 983-91.
50. Tas SW, de Jong EC, Hajji N, et al. Selective inhibition of NFkappaB in dendritic cells by the NEMO-binding domain peptide blocks maturation and prevents T cell proliferation and polarization. Eur J Immunol 2005; 35: 1164-74.
51. Andreakos E, Williams RO, Wales J, Foxwell BM, Feldmann M. Activation of NF-kappaB by the intracellular expression of NFkappaB-inducing kinase acts as a powerful vaccine adjuvant. Proc Natl Acad Sci USA 2006; 103: 14459-64.
52. Ramakrishnan P, Wang W, Wallach D. Receptor-specific signaling for both the alternative and the canonical NF-kappaB activation pathways by NF-kappaB-inducing kinase. Immunity 2004; 21: 477-89.
53. Yoshimura S, Bondeson J, Foxwell BM, Brennan FM, Feldmann M. Effective antigen presentation by dendritic cells is NF-kappaB dependent: coordinate regulation of MHC, co-stimulatory molecules and cytokines. Int Immunol 2001; 13: 675-83.
54. Yoshimura S, Bondeson J, Brennan FM, Foxwell BM, Feldmann M. Antigen presentation by murine dendritic cells is nuclear factorkappa B dependent both in vitro and in vivo. Scand J Immunol 2003; 58: 165-72.
55. Feldmann M, Andreakos E, Smith C, et al. Is NF-kappaB a useful therapeutic target in rheumatoid arthritis? Ann Rheum Dis 2002; 61 Suppl 2: ii13-8.
56. Bonizzi G, Bebien M, Otero DC, et al. Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimers. EMBO J 2004; 23: 4202-10.
57. Gasparini C, Foxwell BM, Feldmann M. RelB/p50 regulates CCL19 production, but fails to promote human DC maturation. Eur J Immunol 2009; 39: 2215-23.
58. Bondeson J, Lauder S, Wainwright S, et al. Adenoviral gene transfer of the endogenous inhibitor IkappaBalpha into human osteoarthritis synovial fibroblasts demonstrates that several matrix metalloproteinases and aggrecanases are nuclear factor-kappaBdependent. J Rheumatol 2007; 34: 523-33.
59. Xia Y, Chen S, Wang Y, et al. RelB modulation of IkappaBalpha stability as a mechanism of transcription suppression of interleukin1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha in fibroblasts. Mol Cell Biol 1999; 19: 7688-96.
60. McMillan DH, Baglole CJ, Thatcher TH, et al. Lung-targeted overexpression of the NF-kappaB member RelB inhibits cigarette smoke-induced inflammation. Am J Pathol 2011; 179: 125-33.
61. Turner JJ, Foxwell KM, Kanji R, et al. Investigation of nuclear factor-kappaB inhibitors and interleukin-10 as regulators of inflammatory signalling in human adipocytes. Clin Exp Immunol 2010; 162: 487-93.
62. Lappas M, Yee K, Permezel M, Rice GE. Sulfasalazine and BAY 11-7082 interfere with the nuclear factor-kappa B and I kappa B kinase pathway to regulate the release of proinflammatory cytokines from human adipose tissue and skeletal muscle in vitro. Endocrinology 2005; 146: 1491-7.
63. Vaira S, Johnson T, Hirbe AC, et al. RelB is the NF-kappaB subunit downstream of NIK responsible for osteoclast differentiation. Proc Natl Acad Sci USA 2008; 105: 3897-902.
64. Soysa NS, Alles N, Weih D, et al. The pivotal role of the alternative NF-kappaB pathway in maintenance of basal bone homeostasis and osteoclastogenesis. J Bone Miner Res 2010; 25: 809-18.
65. Monaco C, Andreakos E, Kiriakidis S, et al. Canonical pathway of nuclear factor kappa B activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis. Proc Natl Acad Sci USA 2004; 101: 5634-9.
66. Amos N, Lauder S, Evans A, Feldmann M, Bondeson J. Adenoviral gene transfer into osteoarthritis synovial cells using the endogenous inhibitor IkappaBalpha reveals that most, but not all, inflammatory and destructive mediators are NFkappaB dependent. Rheumatology (Oxford) 2006; 45: 1201-9.
67. Pande V, Ramos MJ. NF-kappaB in human disease: current inhibitors and prospects for de novo structure based design of inhibitors. Curr Med Chem 2005; 12: 357-74.
68. Karin M, Yamamoto Y, Wang QM. The IKK NF-kappa B system: a treasure trove for drug development. Nat Rev Drug Discov 2004; 3: 17-26.
69. Suzuki J, Ogawa M, Muto S, et al. Novel IkB kinase inhibitors for treatment of nuclear factor-kB-related diseases. Expert Opin Investig Drugs 2011; 20: 395-405.
70. McIntyre KW, Shuster DJ, Gillooly KM, et al. A highly selective inhibitor of I kappa B kinase, BMS-345541, blocks both joint inflammation and destruction in collagen-induced arthritis in mice. Arthritis Rheum 2003; 48: 2652-9.
71. Kwak JH, Jung JK, Lee H. Nuclear factor-kappa B inhibitors; a patent review (2006-2010). Expert Opin Ther Pat 2011; 21: 1897-910.
72. Dai S, Hirayama T, Abbas S, Abu-Amer Y. The IkappaB kinase (IKK) inhibitor, NEMO-binding domain peptide, blocks osteoclastogenesis and bone erosion in inflammatory arthritis. J Biol Chem 2004; 279: 37219-22.
73. Jimi E, Aoki K, Saito H, et al. Selective inhibition of NF-kappa B blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo. Nat Med 2004; 10: 617-24.
74. Chiaravalli J, Fontan E, Fsihi H, et al. Direct inhibition of NFkappaB activation by peptide targeting the NOA ubiquitin binding domain of NEMO. Biochem Pharmacol 2011; 82: 1163-74.
75. Mujtaba T, Dou QP. Advances in the understanding of mechanisms and therapeutic use of bortezomib. Discov Med 2011; 12: 471-80.
76. Liu D, Liu XY, Robinson D, et al. Suppression of Staphylococcal Enterotoxin B-induced Toxicity by a Nuclear Import Inhibitor. J Biol Chem 2004; 279: 19239-46.
77. Torgerson TR, Colosia AD, Donahue JP, Lin YZ, Hawiger J. Regulation of NF-kappa B, AP-1, NFAT, and STAT1 nuclear import in T lymphocytes by noninvasive delivery of peptide carrying the nuclear localization sequence of NF-kappa B p50. J Immunol 1998; 161: 6084-92.
78. Greten FR, Arkan MC, Bollrath J, et al. NF-kappaB is a negative regulator of IL-1beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta. Cell 2007; 130: 918-31.
79. Fong CH, Bebien M, Didierlaurent A, et al. An antiinflammatory role for IKKbeta through the inhibition of classical macrophage activation. J Exp Med 2008; 205: 1269-76.
80. Chen X, Yoza BK, El Gazzar M, et al. RelB sustains IkappaBalpha expression during endotoxin tolerance. Clin Vaccine Immunol 2009; 16: 104-10.
81. Yoza BK, Hu JY, Cousart SL, Forrest LM, McCall CE. Induction of RelB participates in endotoxin tolerance. J Immunol 2006; 177: 4080-5.
82. Cao S, Zhang X, Edwards JP, Mosser DM. NF-kappaB1 (p50) homodimers differentially regulate pro- and anti-inflammatory cytokines in macrophages. J Biol Chem 2006; 281: 26041-50.
83. Saccani A, Schioppa T, Porta C, et al. p50 nuclear factor-kappaB overexpression in tumor-associated macrophages inhibits M1 inflammatory responses and antitumor resistance. Cancer Res 2006; 66: 11432-40.
84. Fei M, Bhatia S, Oriss TB, et al. TNF-alpha from inflammatory dendritic cells (DCs) regulates lung IL-17A/IL-5 levels and neutrophilia versus eosinophilia during persistent fungal infection. Proc Natl Acad Sci USA 2011; 108: 5360-5.
85. Chen X, El Gazzar M, Yoza BK, McCall CE. The NF-kappaB factor RelB and histone H3 lysine methyltransferase G9a directly interact to generate epigenetic silencing in endotoxin tolerance. J Biol Chem 2009; 284: 27857-65.
86. Clohisy JC, Roy BC, Biondo C, et al. Direct inhibition of NFkappa B blocks bone erosion associated with inflammatory arthritis. J Immunol 2003; 171: 5547-53.
87. Takada Y, Singh S, Aggarwal BB. Identification of a p65 peptide that selectively inhibits NF-kappa B activation induced by various inflammatory stimuli and its role in down-regulation of NFkappaB-mediated gene expression and up-regulation of apoptosis. J Biol Chem 2004; 279: 15096-104.
88. Chen LX, Lin L, Wang HJ, et al. Suppression of early experimental osteoarthritis by in vivo delivery of the adenoviral vector-mediated NF-kappaBp65-specific siRNA. Osteoarthritis Cartilage 2008; 16: 174-84.
89. De Vry CG, Prasad S, Komuves L, et al. Non-viral delivery of nuclear factor-kappaB decoy ameliorates murine inflammatory bowel disease and restores tissue homeostasis. Gut 2007; 56: 524-33.
90. Desmet C, Gosset P, Pajak B, et al. Selective blockade of NFkappa B activity in airway immune cells inhibits the effector phase of experimental asthma. J Immunol 2004; 173: 5766-75.
91. Crinelli R, Bianchi M, Gentilini L, Palma L, Magnani M. Locked nucleic acids (LNA): versatile tools for designing oligonucleotide decoys with high stability and affinity. Curr Drug Targets 2004; 5: 745-52.
92. De Stefano D. Oligonucleotides decoy to NF-kappaB: becoming a reality? Discov Med 2011; 12: 97-105.
93. Crinelli R, Carloni E, Menotta M, et al. Oxidized ultrashort nanotubes as carbon scaffolds for the construction of cellpenetrating NF-kappaB decoy molecules. ACS Nano 2010; 4: 2791-803.
94. Famulok M, Hartig JS, Mayer G. Functional aptamers and aptazymes in biotechnology, diagnostics, and therapy. Chem Rev 2007; 107: 3715-43.
95. Lebruska LL, Maher LJ, 3rd. Selection and characterization of an RNA decoy for transcription factor NF-kappa B. Biochemistry 1999; 38: 3168-74.
96. Chan R, Gilbert M, Thompson KM, et al. Co-expression of antiNFkappaB RNA aptamers and siRNAs leads to maximal suppression of NFkappaB activity in mammalian cells. Nucleic Acids Res 2006; 34: e36.
97. Wurster SE, Maher LJ, 3rd. Selection and characterization of antiNF-kappaB p65 RNA aptamers. RNA 2008; 14: 1037-47.
98. Chu TC, Twu KY, Ellington AD, Levy M. Aptamer mediated siRNA delivery. Nucleic Acids Res 2006; 34: e73.
99. Martin E, Capini C, Duggan E, et al. Antigen-specific suppression of established arthritis in mice by dendritic cells deficient in NFkappaB. Arthritis Rheum 2007; 56: 2255-66.
100. Xu MQ, Suo YP, Gong JP, Zhang MM, Yan LN. Prolongation of liver allograft survival by dendritic cells modified with NF-kappaB decoy oligodeoxynucleotides. World J Gastroenterol 2004; 10: 2361-8.
101. Giannoukakis N, Bonham CA, Qian S, et al. Prolongation of cardiac allograft survival using dendritic cells treated with NF-kB decoy oligodeoxyribonucleotides. Mol Ther 2000; 1: 430-7.
102. Pettit AR, Quinn C, MacDonald KP, et al. Nuclear localization of RelB is associated with effective antigen-presenting cell function. J Immunol 1997; 159: 3681-91.
103. Pettit AR, MacDonald KP, O'Sullivan B, Thomas R. Differentiated dendritic cells expressing nuclear RelB are predominantly located in rheumatoid synovial tissue perivascular mononuclear cell aggregates. Arthritis Rheum 2000; 43: 791-800.
104. Li M, Zhang X, Zheng X, et al. Immune modulation and tolerance induction by RelB-silenced dendritic cells through RNA interference. J Immunol 2007; 178: 5480-7.
105. Xia Y, Pauza ME, Feng L, Lo D. RelB regulation of chemokine expression modulates local inflammation. Am J Pathol 1997; 151: 375-87.
106. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-74.
107. Baud V, Karin M. Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov 2009; 8: 33-40.
108. Catley MC, Sukkar MB, Chung KF, et al. Validation of the antiinflammatory properties of small-molecule IkappaB Kinase (IKK)- 2 inhibitors by comparison with adenoviral-mediated delivery of dominant-negative IKK1 and IKK2 in human airways smooth muscle. Mol Pharmacol, 2006; 70: 697-705.
109. Kiriakidis S, Andreakos E, Monaco C, et al. VEGF expression in human macrophages is NF-kappaB-dependent: studies using adenoviruses expressing the endogenous NF-kappaB inhibitor Ikappa- Balpha and a kinase-defective form of the IkappaB kinase 2. J Cell Sci, 2003; 116: 665-74.
110. Saccani S, Pantano S, Natoli G. Modulation of NF-kappaB activity by exchange of dimers. Mol Cell, 2003; 11: 1563-74.