Abstract
The term inflammation was used as early as 1600 BC in Egyptian papyrus writings to describe a complex series of events induced by a wound or an infection. These events can be recognized by the redness, swelling, fever and pain observed, and are now known to reflect the vasodilation, increased capillary permeability and influx of phagocytic cells. Thus, under most circumstances, inflammation is a normal physiological and very beneficial response, employed by our organism to fight infectious agents and protect us from disease. Inflammation involves the activation of both the innate and adaptive branches of the immune system and is under the control of a large number of cellular and molecular components. Major cellular components include B-cells, T-cells, dendritic cells and macrophages (Table 1).
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Download to read the full chapter text
Chapter PDF
References
Agalioti T, Lomvardas S, Parekh B, Yie J, Maniatis T & Thanos D (2000) Ordered recruitment of chromatin modifying and general transcription factors to the IFN-β promoter. Cell 103: 667–678.
Ahmad M, Theofanidis P & Medford RM (1998) Role of activating protein-1 in the regulation of the vascular cell adhesion molecule-1 gene expression by tumor necrosis factor-α. J. Biol. Chem. 273: 4616–4621.
Allport VC, Slater DM, Newton R & Bennett PR (2000) NF-κB and AP-1 are required for cyclo-oxygenase 2 gene expression in amnion epithelial cell line (WISH). Mol. Hum. Reprod. 6: 561–565.
Andreakos E, Foxwell B, Brennan F, Maini R & Feldmann M (2002) Cytokines and anti-cytokine biologicals in autoimmunity: present and future. Cytokine Growth Factor Rev. 13: 299–314.
Asadullah K, Volk HD & Sterry W (2002) Novel immunotherapies for psoriasis. Trends Immunol. 23: 47–53.
Asahara H, Asanuma M, Ogawa N, Nishibayashi S & Inoue H (1995) High DNA-binding activity of transcription factor NF-κB in synovial membranes of patients with rheumatoid arthritis. Biochem. Mol. Biol. Int. 37: 827–832.
Auphan N, DiDonato JA, Rosette C, Helmberg A & Karin M (1995) Immunosuppression by glucocorticoids: inhibition of NF-κB activity through induction of IκB synthesis. Science 270: 286–290.
Baer M, Dillner A, Schwartz RC, Sedon C, Nedospasov S & Johnson PF (1998) Tumor necrosis factor α transcription in macrophages is attenuated by an autocrine factor that preferentially induces NF-κB p50. Mol. Cell. Biol. 18: 5678–5689.
Barger SW, Horster D, Furukawa K, Goodman Y, Krieglstein J & Mattson MP (1995) Tumor necrosis factors α and β protect neurons against amyloid β-peptide toxicity: evidence for involvement of a κB-binding factor and attenuation of peroxide and Ca2+ accumulation. Proc. Natl. Acad. Sci. USA 92: 9328–9332.
Barger SW & Mattson MP (1996) Induction of neuroprotective κB-dependent transcription by secreted forms of the Alzheimer’s β-amyloid precursor. Brain Res. Mol. Brain Res. 40: 116–126.
Barnes PJ & Adcock IM (1997) NF-κB: a pivotal role in asthma and a new target for therapy. Trends Pharmacol. Sci. 18: 46–50.
Barnes PJ & Karin M (1997) Nuclear factor-κB: a pivotal transcription factor in chronic inflammatory diseases. N. Engl. J. Med. 336: 1066–1071.
Beg AA, Sha WC, Bronson RT, Ghosh S & Baltimore D (1995) Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB. Nature 376: 167–170.
Beg AA & Baltimore D (1996) An essential role for NF-κB in preventing TNF-α-induced cell death. Science 274: 782–784.
Belich MP, Salmeron A, Johnston LH & Ley SC (1999) TPL-2 kinase regulates the proteolysis of the NF-AκB-inhibitory protein NF-κB1 p105. Nature 397: 363–368.
Bierhaus A, Schiekofer S, Schwaninger M, Andrassy M, Humpert PM, Chen J, Hong M, Luther T, Henle T, Kloting I, Morcos M, Hofmann M, Tritschler H, Weigle B, Kasper M, Smith M, Perry G, Schmidt AM, Stern DM, Haring HU, Schleicher E & Nawroth PP (2001) Diabetes-associated sustained activation of the transcription factor nuclear factor-κB. Diabetes 50: 2792–2808.
Blackwell TS, Blackwell TR, Holden EP, Christman BW & Christman JW (1996) In vivo antioxidant treatment suppresses nuclear factor-κB activation and neutrophilic lung inflammation. J. Immunol. 157: 1630–1637.
Blackwell TS & Christman JW (1997) The role of nuclear factor-κB in cytokine gene regulation. Am. J. Respir. Cell Mol. Biol. 17: 3–9.
Blackwell TS, Yull FE, Chen CL, Venkatakrishnan A, Blackwell TR, Hicks DJ, Lancaster LH, Christman JW & Kerr LD (1999) Use of genetically altered mice to investigate the role of nuclear factor-κB activation and cytokine gene expression in sepsis-induced ARDS. Chest 116: 73S–74S.
Bogdan C (2001) Nitric oxide and the immune response. Nat. Immunol. 2: 907–916.
Bondeson J, Foxwell B, Brennan F & Feldmann M (1999) Defining therapeutic targets by using adenovirus: blocking NF-κB inhibits both inflammatory and destructive mechanisms in rheumatoid synovium but spares anti-inflammatory mediators. Proc. Natl. Acad. Sci. USA 96: 5668–5673.
Bonetti B, Pohl J, Gao YL & Raine CS (1997) Cell death during autoimmune demyelination: effector but not target cells are eliminated by apoptosis. J. Immunol. 159: 5733–5741.
Bonetti B & Raine CS (1997) Multiple sclerosis: oligodendrocytes display cell death-related molecules in situ but do not undergo apoptosis. Ann. Neurol. 42: 74–84.
Bonetti B, Stegagno C, Cannella B, Rizzuto N, Moretto G & Raine CS (1999) Activation of NF-κB and c-jun transcription factors in multiple sclerosis lesionslmplications for oligodendrocyte pathology. Am. J. Pathol. 155: 1433–1438.
Bours V, Franzoso G, Azarenko V, Park S, Kanno T, Brown K & Siebenlist U (1993) The oncoprotein Bcl-3 directly transactivates through κB motifs via association with DNA-binding p50B homodimers. Cell 72: 729–739.
Brand K, Page S, Rogler G, Bartsch A, Brandi R, Knuechel R, Page M, Kaltschmidt C, Baeuerle PA & Neumeier D (1996) Activated transcription factor nuclear factor-κB is present in the atherosclerotic lesion. J. Clin. Invest. 97: 1715–1722.
Brand K, Eisele T, Kreusel U, Page M, Page S, Haas M, Gerling A, Kaltschmidt C, Neumann FJ, Mackman N, Baeurele PA, Walli AK & Neumeier D (1997) Dysregulation of monocytic nuclear factor-κB by oxidized low-density lipoprotein. Arterioscler. Thromb. Vasc. Biol. 17: 1901–1909.
Caesar I, Gross V, Roth M, Andus T, Schmidt C, Raedsch R, Weber A, Gierend M, Ewe K & Scholmerich J (1997) Treatment of active and postactive ileal and colonic Crohn’s disease with oral pH-modified-release budesonide. German Budesonide Study Group. Hepatogastroenterology 44: 445–451.
Calara F, Dimayuga P, Niemann A, Thyberg J, Diczfalusy U, Witztum JL, Palinski W, Shah PK, Cercek B, Nilsson J & Regnstrom J (1998) An animal model to study local oxidation of LDL and its biological effects in the arterial wall. Arterioscler. Thromb. Vasc. Biol. 18: 884–893.
Caldenhoven E, Liden J, Wissink S, Van de Stolpe A, Raaijmakers J, Koenderman L, Okret S, Gustafsson JA & Van der Saag PT (1995) Negative cross-talk between RelA and the glucocorticoid receptor: a possible mechanism for the antiinflammatory action of glucocorticoids. Mol. Endocrinol. 9: 401–412.
Campbell IK, Gerondakis S, O’Donnell K & Wicks IP (2000) Distinct roles for the NF-κB1 (p50) and c-Rel transcription factors in inflammatory arthritis. J. Clin. Invest. 105: 1799–1806.
Carey M (1998) The enhanceosome and transcriptional synergy. Cell 92: 5–8.
Carter BD, Kaltschmidt C, Kaltschmidt B, Offenhauser N, Bohm-Matthaei R, Baeuerle PA & Barde YA (1996) Selective activation of NF-κB by nerve growth factor through the neurotrophin receptor p75. Science 272: 542–545.
Chang L & Karin M (2001) Mammalian MAP kinase signalling cascades. Nature 410: 37–40.
Chin AI, Dempsey PW, Bruhn K, Miller JF, Xu Y & Cheng G (2002) Involvement of receptor-interacting protein 2 in innate and adaptive immune responses. Nature 416: 190–194.
Christman JW, Lancaster LH & Blackwell TS (1998) Nuclear factor κB: a pivotal role in the systemic inflammatory response syndrome and new target for therapy. Intensive Care Med. 24: 1131–1138.
Christman JW, Sadikot RT & Blackwell TS (2000) The role of nuclear factor-κB in pulmonary diseases. Chest 117: 1482–1487.
Ciechanover A, Gonen H, Bercovich B, Cohen S, Fajerman I, Israel A, Mercurio F, Kahana C, Schwartz AL, Iwai K & Orian A (2001) Mechanisms of ubiquitin-mediated limited processing of the NF-κB1 precursor protein p105. Biochimie 83: 341–349.
Collins T & Cybulsky MI (2001) NF-κB: pivotal mediator or innocent bystander in atherogenesis? J. Clin. Invest. 107: 255–264.
Conron M, Bondeson J, Pantelidis P, Beynon HL, Feldmann M, duBois RM & Foxwell BM (2001) Alveolar macrophages and T cells from sarcoid but not normal lung are permissive to adenovirus infection and allow analysis of NF-κB-dependent signaling pathways. Am. J. Respir. Cell. Mol. Biol. 25: 141–149.
Conron M, Andreakos E, Pantelidis P, Smith C, Beynon HL, Dubois RM & Foxwell BM (2002) Nuclear factor-κB activation in alveolar macrophages requires IκB kinase-β but not nuclear factor-κB inducing kinase. Am. J. Respir. Crit. Care Med. 165: 996–1004.
Couture R, Harrisson M, Vianna RM & Cloutier F (2001) Kinin receptors in pain and inflammation. Eur. J. Pharmacol. 429: 161–176.
Danning CL, Illei GG, Hitchon C, Greer MR, Boumpas DT & Mclnnes IB (2000) Macrophage-derived cytokine and nuclear factor κB p65 expression in synovial membrane and skin of patients with psoriatic arthritis. Arthritis Rheum. 43: 1244–1256.
Darville MI & Eizirik DL (2001) Cytokine induction of Fas gene expression in insulin-producing cells requires the transcription factors NF-κB and C/EBP. Diabetes 50: 1741–1748.
De Bosscher K, Schmitz ML, Vanden Berghe W, Plaisance S, Fiers W & Haegeman G (1997) Gluco-corticoid-mediated repression of nuclear factor-κB-dependent transcription involves direct interference with transactivation. Proc. Natl. Acad. Sci. USA 94: 13504–13509.
de Crombrugghe B, Lefebvre V, Behringer RR, Bi W, Murakami S & Huang W (2000) Transcriptional mechanisms of chondrocyte differentiation. Matrix Biol. 19: 389–394.
Dichtl W, Nilsson L, Goncalves I, Ares MP, Banfi C, Calara F, Hamsten A, Eriksson P & Nilsson J (1999) Very low-density lipoprotein activates nuclear factor-κB in endothelial cells. Circ. Res. 84: 1085–1094.
Donovan CE, Mark DA, He HZ, Liou HC, Kobzik L, Wang Y, De Sanctis GT, Perkins DL & Finn PW (1999) NF-κB/Rel transcription factors: c-Rel promotes airway hyperresponsiveness and allergic pulmonary inflammation. J. Immunol. 163: 6827–6833.
Dumitru CD, Ceci JD, Tsatsanis C, Kontoyiannis D, Stamatakis K, Lin JH, Patriotis C, Jenkins NA, Copeland NG, Kollias G & Tsichlis PN (2000) TNF-α induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway. Cell 103: 1071–1083.
Egan LJ & Sandborn WJ (1998) Inhibition of nuclear factor κB by sulfasalazine: a new target for inflammatory bowel disease therapy? Gastroenterology 115: 1295–1296.
Falvo JV, Uglialoro AM, Brinkman BM, Merika M, Parekh BS, Tsai EY, King HC, Morielli AD, Peralta EG, Maniatis T, Thanos D & Goldfeld AE (2000) Stimulus-specific assembly of enhancer complexes on the tumor necrosis factor α gene promoter. Mol. Cell. Biol. 20: 2239–2247.
Farver CF, Raychaudhuri B, Buhrow LT, Connors MJ & Thomassen MJ (1998) Constitutive NF-κB levels in human alveolar macrophages from normal volunteers. Cytokine 10: 868–871.
Farzaneh-Far A, Davies JD, Braam LA, Spronk HM, Proudfoot D, Chan SW, O’Shaughnessy KM, Weissberg PL, Vermeer C & Shanahan CM (2001) A polymorphism of the human matrix γ-carboxyglutamic acid protein promoter alters binding of an activating protein-1 complex and is associated with altered transcription and serum levels. J. Biol. Chem. 276: 32466–32473.
Feldmann M & Maini RN (2001) Anti-TNFα therapy of rheumatoid arthritis: what have we learned? Annu. Rev. Immunol. 19: 163–196.
Ferrer I, Marti E, Lopez E & Tortosa A (1998) NF-κB immunoreactivity is observed in association with βA4 diffuse plaques in patients with Alzheimer’s disease. Neuropathol. Appl. Neurobiol. 24: 271–277.
Fiocchi C (1998) Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 115: 182–205.
Foxwell B, Browne K, Bondeson J, Clarke C, de Martin R, Brennan F & Feldmann M (1998) Efficient adenoviral infection with IκBα reveals that macrophage tumor necrosis factor α production in rheumatoid arthritis is NF-κB dependent. Proc. Natl. Acad. Sci. USA 95: 8211–8215.
Franzoso G, Bours V, Park S, Tomita-Yamaguchi M, Kelly K & Siebenlist U (1992) The candidate oncoprotein Bcl-3 is an antagonist of p50/NF-κB-mediated inhibition. Nature 359: 339–342.
Franzoso G, Bours V, Azarenko V, Park S, Tomita-Yamaguchi M, Kanno T, Brown K & Siebenlist U (1993) The oncoprotein Bcl-3 can facilitate NF-κB-mediated transactivation by removing inhibiting p50 homodimers from select κB sites. EMBO J. 12: 3893–3901.
Franzoso G, Carlson L, Poljak L, Shores EW, Epstein S, Leonardi A, Grinberg A, Tran T, Scharton-Kersten T, Anver M, Love P, Brown K & Siebenlist U (1998) Mice deficient in nuclear factor (NF)-κB/p52 present with defects in humoral responses germinal center reactions and splenic microarchitecture. J. Exp. Med. 187: 147–159.
Fujihara SM, Cleaveland JS, Grosmaire LS, Berry KK, Kennedy KA, Blake JJ, Loy J, Rankin BM, Ledbetter JA & Nadler SG (2000) A D-amino acid peptide inhibitor of NF-κB nuclear localization is efficacious in models of inflammatory disease. J. Immunol. 165: 1004–1012.
Fujita T, Nolan GP, Liou HC, Scott ML & Baltimore D (1993) The candidate proto-oncogene bcl-3 encodes a transcriptional coactivator that activates through NF-κB p50 homodimers. Genes Dev. 7: 1354–1363.
Funk CD (2001) Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294: 1871–1875.
Geier DL & Miner PB (1992) New therapeutic agents in the treatment of inflammatory bowel disease. Am. J. Med. 93: 199–208.
Ghosh S, May MJ & Kopp EB (1998) NF-κB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 16: 225–260.
Giannoukakis N, Rudert WA, Trucco M & Robbins PD (2000) Protection of human islets from the effects of interleukin-1β by adenoviral gene transfer of an IκB repressor. J. Biol. Chem. 275: 36509–36513.
Grey ST, Arvelo MB, Hasenkamp W, Bach FH & Ferran C (1999) A20 inhibits cytokine-induced apoptosis and nuclear factor κB-dependent gene activation in islets. J. Exp. Med. 190: 1135–1146.
Grilli M, Goffi F, Memo M & Spano P (1996a) Interleukin-lβ and glutamate activate the NF-κB/Rel binding site from the regulatory region of the amyloid precursor protein gene in primary neuronal cultures. J. Biol. Chem. 271: 15002–15007.
Grilli M, Pizzi M, Memo M & Spano P (1996b) Neuroprotection by aspirin and sodium salicylate through blockade of NF-κB activation. Science 274: 1383–1385.
Guerrini L, Blasi F & Denis-Donini S (1995) Synaptic activation of NF-κB by glutamate in cerebellar granule neurons in vitro. Proc. Natl. Acad. Sci. USA 92: 9077–9081.
Gveric D, Kaltschmidt C, Cuzner ML & Newcombe J (1998) Transcription factor NF-κB and inhibitor IκBα are localized in macrophages in active multiple sclerosis lesions. J. Neuropathol. Exp. Neurol. 57: 168–178.
Hajra L, Evans AI, Chen M, Hyduk SJ, Collins T & Cybulsky MI (2000) The NF-κB signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc. Natl. Acad. Sci. USA 97: 9052–9057.
Han Y, Runge MS & Brasier AR (1999) Angiotensin II induces interleukin-6 transcription in vascular Smooth muscle cells through pleiotropic activation of nuclear factor-κB transcription factors. Circ. Res. 84: 695–703.
Han Z, Boyle DL, Manning AM & Firestein GS (1998) AP-1 and NF-κB regulation in rheumatoid arthritis and murine collagen-induced arthritis. Autoimmunity 28: 197–208.
Handel ML, McMorrow LB & Gravallese EM (1995) Nuclear factor-κB in rheumatoid synovium. Localization of p50 and p65. Arthritis Rheum. 38: 1762–1770.
Hart LA, Krishnan VL, Adcock IM, Barnes PJ & Chung KF (1998) Activation and localization of transcription factor nuclear factor-κB in asthma. Am. J. Respir. Crit. Care Med. 158: 1585–1592.
Hayashi T, Sekine T & Okamoto T (1993) Identification of a new serine kinase that activates NFκB by direct phosphorylation. J. Biol. Chem. 268: 26790–26795.
Heck S, Bender K, Kullmann M, Gottlicher M, Herrlich P & Cato AC (1997) IκBα-independent downregulation of NF-κB activity by glucocorticoid receptor. EMBO J. 16: 4698–4707.
Hegazy DM, O’Reilly DA, Yang BM, Hodgkinson AD, Millward BA & Demaine AG (2001) NFκB polymorphisms and susceptibility to type 1 diabetes. Genes Immun. 2: 304–308.
Heimberg H, Heremans Y, Jobin C, Leemans R, Cardozo AK, Darville M & Eizirik DL (2001) Inhibition of cytokine-induced NF-κB activation by adenovirus-mediated expression of a NF-κB super-repressor prevents β-cell apoptosis. Diabetes 50: 2219–2224.
Hilliard B, Samoilova EB, Liu TS, Rostami A & Chen Y (1999) Experimental autoimmune encephalomyelitis in NF-κB-deficient mice: roles of NF-κB in the activation and differentiation of autoreactive T cells. J. Immunol. 163: 2937–2943.
Ho E, Quan N, Tsai YH, Lai W & Bray TM (2001) Dietary zinc supplementation inhibits NFκB activation and protects against chemically induced diabetes in CD1 mice. Exp. Biol. Med. 226: 103–111.
Hofman FM, Hinton DR, Johnson K & Merrill JE (1989) Tumor necrosis factor identified in multiple sclerosis brain. J. Exp. Med. 170: 607–612.
Hofmann MA, Schiekofer S, Kanitz M, Klevesath MS, Joswig M, Lee V, Morcos M, Tritschler H, Ziegler R, Wahl P, Bierhaus A & Nawroth PP (1998) Insufficient glycemie control increases nuclear factor-κB binding activity in peripheral blood mononuclear cells isolated from patients with type 1 diabetes. Diabetes Care 21: 1310–1316.
Hofmann MA, Schiekofer S, Isermann B, Kanitz M, Henkels M, Joswig M, Treusch A, Morcos M, Weiss T, Borcea V, Abdel Khalek AK, Amiral J, Tritschler H, Ritz E, Wahl P, Ziegler R, Bierhaus A & Nawroth PP (1999) Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NF-κB. Diabetologia 42: 222–232.
Hohjoh H & Tokunaga K (2001) Allele-specific binding of the ubiquitous transcription factor OCT-1 to the functional single nucleotide polymorphism (SNP) sites in the tumor necrosis factor-α gene (TNFA) promoter. Genes Immun. 2: 105–109.
Igaz P, Falus A, Glaz E & Racz K (2000) Cytokines in diseases of the endocrine system. Cell Biol. Int 24: 663–668.
Iotsova V, Caamano J, Loy J, Yang Y, Lewin A & Bravo R (1997) Osteopetrosis in mice lacking NF-κB1 and NF-κB2. Nat. Med. 3: 1285–1289.
Kaltschmidt B, Uherek M, Volk B, Baeuerle PA & Kaltschmidt C (1997) Transcription factor NF-κB is activated in primary neurons by amyloid β peptides and in neurons surrounding early plaques from patients with Alzheimer disease. Proc. Natl. Acad. Sci. USA 94: 2642–2647.
Kaltschmidt C, Kaltschmidt B, Neumann H, Wekerle H & Baeuerle PA (1994) Constitutive NF-κB activity in neurons. Mol. Cell. Biol. 14: 3981–3992.
Kaltschmidt C, Kaltschmidt B & Baeuerle PA (1995) Stimulation of ionotropic glutamate receptors activates transcription factor NF-κB in primary neurons. Proc. Natl. Acad. Sci. USA 92: 9618–9622.
Karin M (1999) How NF-κB is activated: the role of the IκB kinase (IKK) complex. Oncogene 18: 6867–6874.
Karin M & Ben-Neriah Y (2000) Phosphorylation meets ubiquitination: the control of NFκB activity. Annu. Rev. Immunol. 18: 621–663.
Keatings VM, Jatakanon A, Worsdell YM & Barnes PJ (1997) Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am. J. Respir. Crit. Care Med. 155: 542–548.
Keifer JA, Guttridge DC, Ashburner BP & Baldwin AS (2001) Inhibition of NF-κB activity by thalidomide through suppression of βB kinase activity. J. Biol. Chem. 276: 22382–22387.
Keller JN, Kindy MS, Holtsberg FW, St Clair DK, Yen HC, Germeyer A, Steiner SM, Bruce-Keller AJ, Hutchins JB & Mattson MP (1998) Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: suppression of peroxynitrite production lipid peroxidation and mitochondrial dysfunction. J. Neurosci. 18: 687–689.
Kelliher MA, Grimm S, Ishida Y, Kuo F, Stanger BZ & Leder P (1998) The death domain kinase RIP mediates the TNF-induced NF-κB signal. Immunity 8: 297–303.
Kieseier BC, Storch MK, Archelos JJ, Martino G & Hartung HP (1999) Effector pathways in immune mediated central nervous system demyelination. Curr. Opin. Neurol. 12: 323–336.
Kim JK, Kim YJ, Fillmore JJ, Chen Y, Moore I, Lee J, Yuan M, Li ZW, Karin M, Perret P, Shoelson SE & Shulman GI (2001) Prevention of fat-induced insulin resistance by salicylate. J. Clin. Invest. 108: 437–446.
Knight JC, Udalova I, Hill AV, Greenwood BM, Peshu N, Marsh K & Kwiatkowski D (1999) A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria. Nat. Genet. 22: 145–150.
Kobayashi K, Inohara N, Hernandez LD, Galan JE, Nunez G, Janeway CA, Medzhitov R & Flavell RA (2002) RICK/RIP2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 416: 194–199.
Kopp E & Ghosh S (1994) Inhibition of NF-κB by sodium salicylate and aspirin. Science 265: 956–959.
Kuhn R, Lohler J, Rennick D, Rajewsky K & Muller W (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75: 263–274.
Kunsch C, Ruben SM & Rosen CA (1992) Selection of optimal κB/Rel DNA-binding motifs: interaction of both subunits of NF-κB with DNA is required for transcriptional activation. Mol. Cell. Biol. 12: 4412–4421.
Landry DB, Couper LL, Bryant SR & Lindner V (1997) Activation of the NF-κB and IκB system in smooth muscle cells after rat arterial injury. Induction of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1. Am. J. Pathol. 151: 1085–1095.
Lavon I, Goldberg I, Amit S, Landsman L, Jung S, Tsuberi BZ, Barshack I, Kopolovic J, Galun E, Bujard H & Ben-Neriah Y (2000) High susceptibility to bacterial infection but no liver dysfunction in mice compromised for hepatocyte NF-κB activation. Nat. Med. 6: 573–577.
Ley K (2001) Pathways and bottlenecks in the web of inflammatory adhesion molecules and chemoattractants. Immunol. Res. 24: 87–95.
Li N & Karin M (1999) Is NF-κB the sensor of oxidative stress? FASEB J. 13: 1137–1143.
Li Q, Van Antwerp D, Mercurio F, Lee KF & Verma IM (1999a) Severe liver degeneration in mice lacking the βB kinase 2 gene. Science 284: 321–325.
Li ZW, Chu W, Hu Y, Delhase M, Deerinck T, Ellisman M, Johnson R & Karin M (1999b) The IKKβ subunit of βB kinase (IKK) is essential for nuclear factor βB activation and prevention of apoptosis. J. Exp. Med. 189: 1839–1845.
Liu ZG, Hsu H, Goeddel DV & Karin M (1996) Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-κB activation prevents cell death. Cell 87: 565–576.
Majumdar S & Aggarwal BB (2001) Methotrexate suppresses NF-κB activation through inhibition of IκBa phosphorylation and degradation. J. Immunol. 167: 2911–2920.
Manna SK, Mukhopadhyay A & Aggarwal BB (2000) Leflunomide suppresses TNF-induced cellular responses: effects on NF-κB activator protein-1: c-Jun N-terminal protein kinase and apoptosis. J. Immunol. 165: 5962–5969.
Marienfeld R, Neumann M, Chuvpilo S, Escher C, Kneitz B, Avots A, Schimpl A & Serfling E (1997) Cyclosporin A interferes with the inducible degradation of NF-κB inhibitors but not with the processing of pl05/NF-κBl in T cells. Eur. J. Immunol. 27: 1601–1609.
Marok R, Winyard PG, Coumbe A, Kus ML, Gaffhey K, Blades S, Mapp PI, Morris CJ, Blake DR, Kaltschmidt C & Baeuerle PA (1996) Activation of the transcription factor nuclear factor-κB in human inflamed synovial tissue. Arthritis Rheum. 39: 583–591.
Martin T, Cardarelli PM, Parry GC, Felts KA & Cobb RR (1997) Cytokine induction of monocyte chemoattractant protein-1 gene expression in human endothelial cells depends on the cooperative action of NF-κB and AP-1. Eur. J. Immunol. 27: 1091–1097.
Matsusaka T, Fujikawa K, Nishio Y, Mukaida N, Matsushima K, Kishimoto T & Akira S (1993) Transcription factors NF-IL6 and NF-κB synergistically activate transcription of the inflammatory cytokines interleukin 6 and interleukin 8. Proc. Natl. Acad. Sci. USA 90: 10193–10197.
Mattson MP, Goodman Y, Luo H, Fu W & Furukawa K (1997) Activation of NF-κB protects hippocampal neurons against oxidative stress-induced apoptosis: evidence for induction of manganese superoxide dismutase and suppression of peroxynitrite production and protein tyrosine nitration. J. Neurosci. Res. 49: 681–697.
Mengshol JA, Vincenti MP, Coon CI, Barchowsky A & Brinckerhoff CE (2000) Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38: c-Jun N-terminal kinase and nuclear factor βB: differential regulation of collagenase 1 and collagenase 3. Arthritis Rheum. 43: 801–811.
Meyer S, Kohler NG & Joly A (1997) Cyclosporine A is an uncompetitive inhibitor of proteasome activity and prevents NF-κB activation. FEBS Lett. 413: 354–358.
Miagkov AV, Kovalenko DV, Brown CE, Didsbury JR, Cogswell JP, Stimpson SA, Baldwin AS & Makarov SS (1998) NF-κB activation provides the potential link between inflammation and hyperplasia in the arthritic joint. Proc. Natl. Acad. Sci. USA 95: 13859–13864.
Mohamed AK, Bierhaus A, Schiekofer S, Tritschler H, Ziegler R & Nawroth PP (1999) The role of oxidative stress and NF-κB activation in late diabetic complications. Biofactors 10: 157–167.
Morigi M, Angioletti S, Imberti B, Donadelli R, Micheletti G, Figliuzzi M, Remuzzi A, Zoja C & Remuzzi G (1998) Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-κB-dependent fashion. J. Clin. Invest. 101: 1905–1915.
Mortensen RF (2001) C-reactive protein inflammation and innate immunity. Immunol. Res. 24: 163–176.
Murakami S, Lefebvre V & de Crombrugghe B (2000) Potent inhibition of the master chondrogenic factor Sox9 gene by interleukin-1 and tumor necrosis factor-α. J. Biol. Chem. 275: 3687–3692.
Neish AS, Khachigian LM, Park A, Baichwal VR & Collins T (1995a) Spl is a component of the cytokine-inducible enhancer in the promoter of vascular cell adhesion molecule-1. J. Biol. Chem. 270: 28903–28909.
Neish AS, Read MA, Thanos D, Pine R, Maniatis T & Collins T (1995b) Endothelial interferon regulatory factor 1 cooperates with NF-κB as a transcriptional activator of vascular cell adhesion molecule 1. Mol. Cell. Biol. 15: 2558–2569.
Neurath MF, Pettersson S, Meyer zum Buschenfelde KH & Strober W (1996) Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-κB abrogates established experimental colitis in mice. Nat. Med. 2: 998–1004.
Neurath MF & Pettersson S (1997) Predominant role of NF-κB p65 in the pathogenesis of chronic intestinal inflammation. Immunobiology 198: 91–98.
Nikolaus S, Raedler A, Kuhbacker T, Sfikas N, Folsch UR & Schreiber S (2000) Mechanisms in failure of infliximab for Crohn’s disease. Lancet 356: 1475–1479.
Norbiato G, Bevilacqua M, Vago T & Clerici M (1997) Glucocorticoids and Th-1: Th-2 type cytokines in rheumatoid arthritis osteoarthritis asthma atopic dermatitis and AIDS. Clin. Exp. Rheumatol. 15: 315–323.
O’Neill LA & Kaltschmidt C (1997) NF-κB: a crucial transcription factor for glial and neuronal cell function. Trends Neurosci. 20: 252–258.
Pahan K & Schmid M (2000) Activation of nuclear factor-κB in the spinal cord of experimental allergic encephalomyelitis. Neurosci. Lett. 287: 17–20.
Pahl HL (1999) Activators and target genes of Rel/NF-κB transcription factors. Oncogene 18: 6853–6866.
Palombella VJ, Conner EM, Fuseler JW, Destree A, Davis JM, Laroux FS, Wolf RE, Huang J, Brand S, Elliott PJ, Lazarus D, McCormack T, Parent L, Stein R, Adams J & Grisham MB (1998) Role of the proteasome and NF-κB in streptococcal cell wall-induced polyarthritis. Proc. Natl. Acad. Sci. USA 95: 15671–15676.
Pan J & McEver RP (1995) Regulation of the human P-selectin promoter by Bcl-3 and specific homo-dimeric members of the NF-κB/Rel family. J. Biol. Chem. 270: 23077–23083.
Park BH & Park JW (2001) The protective effect of Amomum xanthoides extract against alloxan-induced diabetes through the suppression of NFκB activation. Exp. Mol. Med. 33: 64–68.
Pierce JW, Read MA, Ding H, Luscinskas FW & Collins T (1996) Salicylates inhibit IκBα phosphorylation endothelial-leukocyte adhesion molecule expression and neutrophil transmigration. J. Immunol. 156: 3961–3969.
Poligone B, Weaver DJ, Sen P, Baldwin AS & Tisch R (2002) Elevated NF-κB activation in non-obese diabetic mouse dendritic cells results in enhanced APC function. J. Immunol. 168: 188–196.
Price SJ, Greaves DR & Watkins H (2001) Identification of novel functional genetic variants in the human matrix metalloproteinase-2 gene: role of Spl in allele-specific transcriptional regulation. J. Biol. Chem. 276: 7549–7558.
Pueyo ME, Gonzalez W, Nicoletti A, Savoie F, Arnal JF & Michel JB (2000) Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor-κB activation induced by intracellular oxidative stress. Arterioscler. Thromb. Vasc. Biol. 20: 645–651.
Quan N, Ho E, La W, Tsai YH & Bray T (2001) Administration of NF-κB decoy inhibits pancreatic activation of NF-κB and prevents diabetogenesis by alloxan in mice. FASEB J. 15: 1616–1618.
Roebuck KA (1999) Regulation of interleukin-8 gene expression. J. Interferon Cytokine Res. 19: 429–438.
Rogler G, Brand K, Vogl D, Page S, Hofmeister R, Andus T, Knuechel R, Baeuerle PA, Scholmerich J & Gross V (1998) Nuclear factor κB is activated in macrophages and epithelial cells of inflamed intestinal mucosa. Gastroenterology 115: 357–369.
Ruddle NH (1999) Lymphoid neo-organogenesis: lymphotoxin’s role in inflammation and development. Immunol. Res. 19: 119–125.
Rudolph D, Yeh WC, Wakeham A, Rudolph B, Nallainathan D, Potter J, Elia AJ & Mak TW (2000) Severe liver degeneration and lack of NF-κB activation in NEMO/IKKγ-deficient mice. Genes Dev. 14: 854–862.
Saccani S, Pantano S & Natoli G (2001) Two waves of nuclear factor κB recruitment to target promoters. J. Exp. Med. 193: 1351–1359.
Saccani S, Pantano S & Natoli G (2002) p38-Dependent marking of inflammatory genes for increased NF-κB recruitment. Nat Immunol. 3: 69–75.
Scheinman RI, Cogswell PC, Lofquist AK & Baldwin AS (1995a) Role of transcriptional activation of IκBα in mediation of immunosuppression by glucocorticoids. Science 270: 283–286.
Scheinman RI, Gualberto A, Jewell CM, Cidlowski JA & Baldwin AS (1995b) Characterization of mechanisms involved in transrepression of NF-κB by activated glucocorticoid receptors. Mol. Cell. Biol. 15: 943–953.
Schmidt AM, Yan SD, Wautier JL & Stern D (1999) Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ. Res. 84: 489–497.
Schmitz ML & Baeuerle PA (1991) The p65 subunit is responsible for the strong transcription activating potential of NF-κB. EMBO J. 10: 3805–3817.
Schmitz ML, Bacher S & Kracht M (2001) IκB-independent control of NF-κB activity by modulatory phosphorylations. Trends Biochem. Sci. 26: 186–190.
Schreck R, Albermann K & Baeuerle PA (1992) Nuclear factor κB: an oxidative stress-responsive transcription factor of eukaryotic cells (a review). Free Radic. Res. Commun. 17: 221–237.
Schreiber S, Nikolaus S & Hampe J (1998) Activation of nuclear factor κB inflammatory bowel disease. Gut 42: 477–484.
Schwartz MD, Moore EE, Moore FA, Shenkar R, Moine P, Haenel JB & Abraham E (1996) Nuclear factor-κB is activated in alveolar macrophages from patients with acute respiratory distress syndrome. Crit. Care Med. 24: 1285–1292.
Seetharaman R, Mora AL, Nabozny G, Boothby M & Chen J (1999) Essential role of T cell NF-κB activation in collagen-induced arthritis. J. Immunol. 163: 1577–1583.
Selmaj K, Raine CS, Cannella B & Brosnan CF (1991) Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. J. Clin. Invest. 87: 949–954.
Senftleben U, Cao Y, Xiao G, Greten FR, Krahn G, Bonizzi G, Chen Y, Hu Y, Fong A, Sun SC & Karin M (2001) Activation by IKKα of a second evolutionary conserved NF-κB signaling pathway. Science 293: 1495–1499.
Sha WC, Liou HC, Tuomanen EI & Baltimore D (1995) Targeted disruption of the p50 subunit of NF-κB leads to multifocal defects in immune responses. Cell 80: 321–330.
Shenkar R & Abraham E (1997) Hemorrhage induces rapid in vivo activation of CREB and NF-κB in murine intraparenchymal lung mononuclear cells. Am. J. Respir. Cell Mol. Biol. 16: 145–152.
Simeonidis S, Liang S, Chen G & Thanos D (1997) Cloning and functional characterization of mouse IκBε. Proc. Natl. Acad. Sci. USA 94: 14372–14377.
Smith C, Andreakos E, Crawley JB, Brennan FM, Feldmann M & Foxwell BM (2001) NF-κB-inducing kinase is dispensable for activation of NF-κB in inflammatory settings but essential for lymphotoxin β receptor activation of NF-κB in primary human fibroblasts. J. Immunol. 167: 5895–5903.
Stein B, Baldwin AS, Ballard DW, Greene WC, Angel P & Herrlich P (1993) Cross-coupling of the NF-κB p65 and Fos/Jun transcription factors produces potentiated biological function. EMBO J. 12: 3879–3891.
Tanaka M, Fuentes ME, Yamaguchi K, Durnin MH, Dalrymple SA, Hardy KL & Goeddel DV (1999) Embryonic lethality liver degeneration and impaired NF-κB activation in IKK-β-deficient mice. Immunity 10: 421–429.
Terai K, Matsuo A & McGeer PL (1996) Enhancement of immunoreactivity for NF-κB in the hippocampal formation and cerebral cortex of Alzheimer’s disease. Brain Res. 735: 159–168.
Thanos D & Maniatis T (1995) Virus induction of human IFNβ gene expression requires the assembly of an enhanceosome. Cell 83: 1091–1100.
Thompson AB, Robbins RA, Romberger DJ, Sisson JH, Spurzem JR, Teschler H & Rennard SI (1995a) Immunological functions of the pulmonary epithelium. Eur. Respir. J. 8: 127–149.
Thompson JE, Phillips RJ, Erdjument-Bromage H, Tempst P & Ghosh S (1995b) IκB-β regulates the persistent response in a biphasic activation of NF-κB. Cell 80: 573–582.
Tomita T, Takeuchi E, Tomita N, Morishita R, Kaneko M, Yamamoto K, Nakase T, Seki H, Kato K, Kaneda Y & Ochi T (1999) Suppressed severity of collagen-induced arthritis by in vivo transfection of nuclear factor κB decoy oligodeoxynucleotides as a gene therapy. Arthritis Rheum. 42: 2532–2542.
Tsao PW, Suzuki T, Totsuka R, Murata T, Takagi T, Ohmachi Y, Fujimura H & Takata I (1997) The effect of dexamethasone on the expression of activated NF-κB in adjuvant arthritis. Clin. Immunol. Immunopathol. 83: 173–178.
Udalova IA, Richardson A, Denys A, Smith C, Ackerman H, Foxwell B & Kwiatkowski D (2000) Functional consequences of a polymorphism affecting NF-κB p50–p50 binding to the TNF promoter region. Mol. Cell. Biol. 20: 9113–9119.
Udalova IA, Mott R, Field D & Kwiatkowski D (2002a) Quantitative prediction of NF-κB DNA-protein interactions. Proc. Natl. Acad. Sci. USA 99: 8167–8172.
Udalova IA, Richardson A, Ackerman H, Wordsworth P & Kwiatkowski D (2002b) Association of accelerated erosive rheumatoid arthritis with a polymorphism that alters NF-κB binding to the TNF promoter region. Rheumatology 41: 830–831.
Van Antwerp DJ, Martin SJ, Kafri T, Green DR & Verma IM (1996) Suppression of TNF-α-induced apoptosis by NF-κB. Science 274: 787–789.
van Heel DA, Udalova IA, De Silva AP, McGovern DP, Kinouchi Y, Hull J, Lench NJ, Cardon LR, Carey AH, Jewell DP & Kwiatkowski D (2002) Inflammatory bowel disease is associated with a TNF polymorphism that affects an interaction between the OCT1 and NF-κB transcription factors. Hum. Mol. Genet. 11: 1281–1289.
Venkataraman L, Burakoff SJ & Sen R (1995) FK506 inhibits antigen receptor-mediated induction of c-rel in B and T lymphoid cells. J. Exp. Med. 181: 1091–1099.
Wahl C, Liptay S, Adler G & Schmid RM (1998) Sulfasalazine: a potent and specific inhibitor of nuclear factor βB. J. Clin. Invest. 101: 1163–1174.
Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ & Selkoe DJ (2002) Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416: 535–539.
Wang CY, Mayo MW & Baldwin AS (1996) TNF-and cancer therapy-induced apoptosis: potentiation by inhibition of NF-κB. Science 274: 784–787.
Wang D, Westerheide SD, Hanson JL & Baldwin AS (2000) Tumor necrosis factor α-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II. J. Biol. Chem. 275: 32592–32597.
Weaver DJ, Poligone B, Bui T, Abdel-Motal UM, Baldwin AS & Tisch R (2001) Dendritic cells from nonobese diabetic mice exhibit a defect in NF-κB regulation due to a hyperactive IκB kinase. J. Immunol. 167: 1461–1468.
Weih F, Durham SK, Barton DS, Sha WC, Baltimore D & Bravo R (1997) p50-NF-κB complexes partially compensate for the absence of RelB: severely increased pathology in p50−/−relB−/− double-knockout mice. J. Exp. Med. 185: 1359–1370.
Weingarten P, Bermak J & Zhou QY (2001) Evidence for non-oxidative dopamine cytotoxicity: potent activation of NF-κB and lack of protection by anti-oxidants. J. Neurochem. 76: 1794–1804.
Welch GN & Loscalzo J (1998) Homocysteine and atherothrombosis. N. Engl. J. Med. 338: 1042–1050.
Whiteside ST, Epinat JC, Rice NR & Israel A (1997) IκBε, a novel member of the IκB family, controls RelA and cRel NF-κB activity. EMBO J. 16: 1413–1426.
Whitley MZ, Thanos D, Read MA, Maniatis T & Collins T (1994) A striking similarity in the organization of the E-selectin and β interferon gene promoters. Mol. Cell. Biol. 14: 6464–6475.
Wilckens T & De Rijk R (1997) Glucocorticoids and immune function: unknown dimensions and new frontiers. Immunol. Today 18: 418–424.
Wilson SH, Caplice NM, Simari RD, Holmes DR, Carlson PJ & Lerman A (2000) Activated nuclear factor-κB is present in the coronary vasculature in experimental hypercholesterolemia. Atherosclerosis 148: 23–30.
Woodroofe MN & Cuzner ML (1993) Cytokine mRNA expression in inflammatory multiple sclerosis lesions: detection by non-radioactive in situ hybridization. Cytokine 5: 583–588.
Wulczyn FG, Naumann M & Scheidereit C (1992) Candidate proto-oncogene bcl-3 encodes a subunit-specific inhibitor of transcription factor NF-κB. Nature 358: 597–599.
Xiao G, Harhaj EW & Sun SC (2001) NF-κB-inducing kinase regulates the processing of NF-κB2 p100. Mol. Cell 7: 401–409.
Yan SD, Yan SF, Chen X, Fu J, Chen M, Kuppusamy P, Smith MA, Perry G, Godman GC, Nawroth P, Zweiter JL & Stern D (1995) Non-enzymatically glycated tau in Alzheimer’s disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid β- peptide. Nat. Med. 1: 693–699.
Yang JP, Merin JP, Nakano T, Kato T, Kitade Y & Okamoto T (1995) Inhibition of the DNA-binding activity of NF-κB by gold compounds in vitro. FEBS Lett. 361: 89–96.
Yang L, Cohn L, Zhang DH, Homer R, Ray A & Ray P (1998) Essential role of nuclear factor κB in the induction of eosinophilia in allergic airway inflammation. J. Exp. Med. 188: 1739–1750.
Yin MJ, Yamamoto Y & Gaynor RB (1998) The anti-inflammatory agents aspirin and salicylate inhibit the activity of IκB kinase-β. Nature 396: 77–80.
Zhong H, SuYang H, Erdjument-Bromage H, Tempst P & Ghosh S (1997) The transcriptional activity of NF-κB is regulated by the IκB-associated PKAc subunit through a cyclic AMP-independent mechanism. Cell 89: 413–424.
Zollner TM, Podda M, Pien C, Elliott PJ, Kaufmann R & Boehncke WH (2002) Proteasome inhibition reduces superantigen-mediated T cell activation and the severity of psoriasis in a SCID-hu model. J. Clin. Invest. 109: 671–679.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Andreakos, E., Udalova, I., Sacre, S., Foxwell, B.M. (2003). The Role of NF-κB in Inflammatory Diseases. In: Beyaert, R. (eds) Nuclear Factor кB. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-0163-2_13
Download citation
DOI: https://doi.org/10.1007/978-94-010-0163-2_13
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-3983-3
Online ISBN: 978-94-010-0163-2
eBook Packages: Springer Book Archive