Skip to main content
Log in

NF-κB, a pivotal transcription factor in silica-induced diseases

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Inhalation of silica in a number of occupational settings can result in debilitating and costly lung disease. It is thought that the pathological replacement of functional lung tissue with fibrotic lesions in silica-induced lung disease is the result of chronic inflammation mediated by products of the silica-exposed alveolar macrophage. In particular, inflammatory cytokines, growth factors and reactive oxygen species have been implicated in many acute and chronic inflammatory lung diseases. Pharmacological intervention to modify the production of these mediators has been shown to ameliorate several of these disease processes. Recent studies have demonstrated that the production of these inflammatory mediators is altered as a result of the activation of nuclear factor-κB (NF-κB). NF-κB is a pivotal transcription factor activated by silica in macrophages and other types of lung cells. The understanding of how silica induces NF-κB activation and what signaling pathways are involved in this silica-induced NF-κB activation is important and should provide valuable new information related to both the etiology and potential treatment of silica-related lung diseases. This review summarizes the molecular mechanisms involved in silica-induced NF-κB activation and discusses the importance of NF-κB as a critical transcription factor in mediating silica-induced lung diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Chen F, Sun SC, Kuhn DC, Gaydos LJ, Demers LM: Essential role of NF-κB activation in silica-induced inflammatory mediator production in macrophages. Biochem Biophys Res Commun 214: 985–992, 1995

    Article  PubMed  Google Scholar 

  2. Chen F, Kuhn DC, Sun SC, Gaydos LJ, Demers LM: Dependence and reversal of nitric oxide production on NF-κB in silica and lipopolysaccharide-induced macrophages. Biochem Biophys Res Commun 214: 839–846, 1995

    PubMed  Google Scholar 

  3. Chen F, Castranova V, Shi X, Demers LM: New insights into the role of nuclear factor-κB, a ubiquitous transcription factor in the initiation of diseases. Clin Chem 45: 7–17, 1999

    PubMed  Google Scholar 

  4. Baldwin AS Jr: The NF-κB and IκB proteins: New discoveries and insights. Annu Rev Immunol 14: 649–683, 1996

    Article  PubMed  Google Scholar 

  5. Karin M, Delhase M: The IκB kinase [IKK] and NF-κB: Key elements of proinflammatory signalling. Semin Immunol 12: 85–98, 2000

    Article  PubMed  Google Scholar 

  6. Karin M, Ben-Neriah Y: Phosphorylation meets ubiquitination: The control of NF-κB activity. Annu Rev Immunol 18: 621–663, 2000

    PubMed  Google Scholar 

  7. Mayo MW, Baldwin AS: The transcription factor NF-κB: Control of oncogenesis and cancer therapy resistance. Biochim Biophys Acta 1470: M55–62, 2000

    PubMed  Google Scholar 

  8. Sen R, Baltimore D: Inducibility of γ immunoglobulin enhancer-binding protein NF-κB by a posttranslational mechanism. Cell 47: 921–928, 1986

    Article  PubMed  Google Scholar 

  9. Kopp EB, Ghosh S: NF-κB and rel proteins in innate immunity. Adv Immunol 58: 1–27, 1995

    PubMed  Google Scholar 

  10. Zhang G, Ghosh S: Toll-like receptor-mediated NF-κB activation: A phylogenetically conserved paradigm in innate immunity. J Clin Invest 107: 13–19, 2001

    PubMed  Google Scholar 

  11. Chen ZJ, Parent L, Maniatis T: Site-specific phosphorylation of IκBγ by a novel ubiquitination-dependent protein kinase activity. Cell 84: 853–862, 1996

    PubMed  Google Scholar 

  12. Orian A, Gonen H, Bercovich B, Fajerman I, Eytan E, Israel A, Mercurio F, Iwai K, Schwartz AL, Ciechanover A: SCF-β-TrCP ubiquitin ligase-mediated processing of NF-κB p105 requires phosphorylation of its C-terminus by IκB kinase. EMBO J 19: 2580–2591, 2000

    PubMed  Google Scholar 

  13. Strack P, Caligiuri M, Pelletier M, Boisclair M, Theodoras A, Beer-Romero P, Glass S, Parsons T, Copeland RA, Auger KR, Benfield P, Brizuela L, Rolfe M: SCF-β-TrCP and phosphorylation dependent ubiquitinationof IκB alpha catalyzed by Ubc3 and Ubc4. Oncogene 19: 3529–3536, 2000

    Article  PubMed  Google Scholar 

  14. Neish AS, Gewirtz AT, Zeng H, Young AN, Hobert ME, Karmali V, Rao AS, Madara JL: Prokaryotic regulation of epithelial responses by inhibition of IκBα ubiquitination. Science 289: 1560–1563, 2000

    PubMed  Google Scholar 

  15. Palombella VJ, Rando OJ, Goldberg AL, Maniatis T: The ubiquitinproteasome pathway is required for processing the NF-κB1 precursor protein and the activation of NF-κB. Cell 78: 773–785, 1994

    Article  PubMed  Google Scholar 

  16. Woronicz JD, Gao X, Cao Z, Rothe M, Goeddel DV: IκB kinasebeta: NF-κB activation and complex formation with IκB kinase-α and NIK. Science 278: 866–869, 1997

    Article  PubMed  Google Scholar 

  17. Mercurio F, Zhu H, Murray BW, Shevchenko A, Bennett BL, Li J, Young DB, Barbosa M, Mann M, Manning A, Rao A: IKK-1 and IKK-2: Cytokine-activated IκB kinases essential for NF-κB activation. Science 278: 860–866, 1997

    PubMed  Google Scholar 

  18. Cohen L, Henzel WJ, Baeuerle PA: IKAP is a scaffold protein of the IκB kinase complex. Nature 395: 292–296, 1998

    Article  PubMed  Google Scholar 

  19. Krappmann D, Hatada EN, Tegethoff S, Li J, Klippel A, Giese K, Baeuerle PA, Scheidereit C: The IκB kinase [IKK] complex is tripartite and contains IKK gamma but not IKAP as a regular component. J Biol Chem 275: 29779–29787, 2000

    PubMed  Google Scholar 

  20. Leonardi A, Chariot A, Claudio E, Cunningham K, Siebenlist U: CIKS, a connection to IκB kinase and stress-activated protein kinase. Proc Natl Acad Sci USA 97: 10494–10499, 2000

    Article  PubMed  Google Scholar 

  21. Li X, Commane M, Nie H, Hua X, Chatterjee-Kishore M, Wald D, Haag M, Stark GR: Act1, an NF-κB-activating protein. Proc Natl Acad Sci USA 97: 10489–10493, 2000

    PubMed  Google Scholar 

  22. Hu Y, Baud V, Oga T, Kim KI, Yoshida K, Karin M: IKKα controls formation of the epidermis independently of NF-κB. Nature 410: 710–714, 2001

    Article  PubMed  Google Scholar 

  23. Peters RT, Liao SM, Maniatis T: IKKε is part of a novel PMA-inducible IκB kinase complex. Mol Cell 5: 513–522, 2000

    PubMed  Google Scholar 

  24. Shimada T, Kawai T, Takeda K, Matsumoto M, Inoue J, Tatsumi Y, Kanamaru A, Akira S: IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IκB kinases. Int Immunol 11: 1357–1362, 1999

    PubMed  Google Scholar 

  25. Pomerantz JL, Baltimore D: NF-κB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. Embo J 18: 6694–6704, 1999

    Article  PubMed  Google Scholar 

  26. Israel A: The IKK complex: An integrator of all signals that activate NF-κB? Trends Cell Biol 10: 129–133, 2000

    Article  PubMed  Google Scholar 

  27. Tojima Y, Fujimoto A, Delhase M, Chen Y, Hatakeyama S, Nakayama K, Kaneko Y, Nimura Y, Motoyama N, Ikeda K, Karin M, Nakanishi M: NAK is an IκB kinase-activating kinase. Nature 404: 778–782, 2000

    PubMed  Google Scholar 

  28. Chen F, Lu Y, Kuhn DC, Maki M, Shi X, Sun SC, Demers LM: Calpain contributes to silica-induced IκBá degradation and nuclear factor-kappa B activation. Arch Biochem Biophys 342: 383–388, 1997

    PubMed  Google Scholar 

  29. Chen F, Demers LM, Vallyathan V, Lu Y, Castranova V, Shi X: Impairment of NF-κB activation and modulation of gene expression by calpastatin. Am J Physiol Cell Physiol 279: C709–716, 2000

    PubMed  Google Scholar 

  30. Baud V, Liu ZG, Bennett B, Suzuki N, Xia Y, Karin M: Signaling by proinflammatory cytokines: Oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain. Genes Dev 13: 1297–1308, 1999

    PubMed  Google Scholar 

  31. Guha M, Mackman N: LPS induction of gene expression in human monocytes. Cell Signal 13: 85–94, 2001

    Article  PubMed  Google Scholar 

  32. Carter RS, Geyer BC, Xie M, Acevedo-Suarez CA, Ballard DW: Persistent activation of NF-κB by the tax transforming protein involves chronic phosphorylation of IκB kinase subunits IKKβ and IKKα. J Biol Chem 26: 26, 2001

    Google Scholar 

  33. Jeang K: Functional activities of the human T-cell leukemia virus type I Tax oncoprotein: Cellular signaling through NF-κB. Cytokine Growth Factor Rev 12: 207–217, 2001

    Article  PubMed  Google Scholar 

  34. Lin X, Cunningham ET Jr, Mu Y, Geleziunas R, Greene WC: The proto-oncogene Cot kinase participates in CD3/CD28 induction of NF-κB acting through the NF-κB-inducing kinase and IκB kinases. Immunity 10: 271–280, 1999

    PubMed  Google Scholar 

  35. Demers LM, Kuhn DC: Influence of mineral dusts on metabolism of arachidonic acid by alveolar macrophage. Environ Health Perspect 102 Suppl 10: 97–100, 1994

    Google Scholar 

  36. Huffman LJ, Judy DJ, Castranova V: Regulation of nitric oxide production by rat alveolar macrophages in response to silica exposure. J Toxicol Environ Health A 53: 29–46, 1998

    PubMed  Google Scholar 

  37. Davis GS, Pfeiffer LM, Hemenway DR: Persistent overexpression of interleukin-1α and tumor necrosis factor-β in murine silicosis. J Environ Pathol Toxicol Oncol 17: 99–114, 1998

    PubMed  Google Scholar 

  38. Gosset P, Lassalle P, Vanhee D, Wallaert B, Aerts C, Voisin C, Tonnel AB: Production of tumor necrosis factor-alpha and interleukin-6 by human alveolar macrophages exposed in vitro to coal mine dust. Am J Respir Cell Mol Biol 5: 431–436, 1991

    PubMed  Google Scholar 

  39. Imbert V, Rupec RA, Livolsi A, Pahl HL, Traenckner EB, Mueller-Dieckmann C, Farahifar D, Rossi B, Auberger P, Baeuerle PA, Peyron JF: Tyrosine phosphorylation of IκBá activates NF-κB without proteolytic degradation of IκBá. Cell 86: 787–798, 1996

    Article  PubMed  Google Scholar 

  40. Shi X, Dong Z, Huang C, Ma W, Liu K, Ye J, Chen F, Leonard SS, Ding M, Castranova V, Vallyathan V: The role of hydroxyl radical as a messenger in the activation of nuclear transcription factor NF-κB. Mol Cell Biochem 194: 63–70, 1999

    PubMed  Google Scholar 

  41. Shi X, Ding M, Dong Z, Chen F, Ye J, Wang S, Leonard SS, Castranova V, Vallyathan V: Antioxidant properties of aspirin: Characterization of the ability of aspirin to inhibit silica-induced lipid peroxidation, DNA damage, NF-κB activation, and TNFα production. Mol Cell Biochem 199: 93–102, 1999

    PubMed  Google Scholar 

  42. Garban HJ, Bonavida B: Nitric oxide disrupts H2O2-dependent activation of nuclear factor κB. Role in sensitization of human tumor cells to tumor necrosis factor-alpha-induced cytotoxicity. J Biol Chem 276: 8918–8923, 2001

    PubMed  Google Scholar 

  43. Chen F, Lu Y, Demers LM, Rojanasakul Y, Shi X, Vallyathan V, Castranova V: Role of hydroxyl radical in silica-induced NF-κB activation in macrophages. Ann Clin Lab Sci 28: 1–13, 1998

    PubMed  Google Scholar 

  44. Ding M, Shi X, Dong Z, Chen F, Lu Y, Castranova V, Vallyathan V: Freshly fractured crystalline silica induces activator protein-1 activation through ERKs and p38 MAPK. J Biol Chem 274: 30611–30616, 1999

    PubMed  Google Scholar 

  45. Shukla A, Timblin CR, Hubbard AK, Bravman J, Mossman BT: Silicainduced activation of c-Jun-NH2-terminal amino kinases, protracted expression of the activator protein-1 proto-oncogene, fra-1, and Sphase alterations are mediated via oxidative stress. Cancer Res 61: 1791–1795, 2001

    PubMed  Google Scholar 

  46. Li N, Karin M: Is NF-κB the sensor of oxidative stress? FASEB J 13: 1137–1143, 1999

    PubMed  Google Scholar 

  47. Han Y, Weinman S, Boldogh I, Walker RK, Brasier AR: Tumor necrosis factor-α-inducible IκBα proteolysis mediated by cytosolic m-calpain. A mechanism parallel to the ubiquitin-proteasome pathway for nuclear factor-κB activation. J Biol Chem 274: 787–794, 1999

    PubMed  Google Scholar 

  48. Baghdiguian S, Martin M, Richard I, Pons F, Astier C, Bourg N, Hay RT, Chemaly R, Halaby G, Loiselet J, Anderson LV, Lopez de Munain A, Fardeau M, Mangeat P, Beckmann JS, Lefranc G: Calpain 3 deficiency is associated with myonuclear apoptosis and profound perturbation of the IκBα/NF-κB pathway in limb-girdle muscular dystrophy type 2A. Nat Med 5: 503–511, 1999

    PubMed  Google Scholar 

  49. Miyamoto S, Seufzer BJ, Shumway SD: Novel IκBα proteolytic pathway in WEHI231 immature B cells. Mol Cell Biol 18: 19–29, 1998

    PubMed  Google Scholar 

  50. Shumway SD, Maki M, Miyamoto S: The PEST domain of IκBα is necessary and sufficient for in vitro degradation by µ-calpain. J Biol Chem 274: 30874–30881, 1999

    PubMed  Google Scholar 

  51. Wang KK, Yuen PW: Calpain inhibition: An overview of its therapeutic potential. Trends Pharmacol Sci 15: 412–419, 1994

    PubMed  Google Scholar 

  52. Potter DA, Tirnauer JS, Janssen R, Croall DE, Hughes CN, Fiacco KA, Mier JW, Maki M, Herman IM: Calpain regulates actin remodeling during cell spreading. J Cell Biol 141: 647–662, 1998

    PubMed  Google Scholar 

  53. Tanabe F, Cui SH, Ito M: Ceramide promotes calpain-mediated proteolysis of protein kinase Cβ in murine polymorphonuclear leukocytes. Biochem Biophys Res Commun 242: 129–133, 1998

    Article  PubMed  Google Scholar 

  54. Kavita U, Mizel SB: Differential sensitivity of interleukin-1α and-β precursor proteins to cleavage by calpain, a calcium-dependent protease. J Biol Chem 270: 27758–27765, 1995

    PubMed  Google Scholar 

  55. Gonen H, Shkedy D, Barnoy S, Kosower NS, Ciechanover A: On the involvement of calpains in the degradation of the tumor suppressor protein p53. FEBS Lett 406: 17–22, 1997

    PubMed  Google Scholar 

  56. Kubbutat MH, Vousden KH: Proteolytic cleavage of human p53 by calpain: A potential regulator of protein stability. Mol Cell Biol 17: 460–468, 1997

    PubMed  Google Scholar 

  57. Pariat M, Carillo S, Molinari M, Salvat C, Debussche L, Bracco L, Milner J, Piechaczyk M: Proteolysis by calpains: A possible contribution to degradation of p53. Mol Cell Biol 17: 2806–2815, 1997

    PubMed  Google Scholar 

  58. Zhang W, Lu Q, Xie ZJ, Mellgren RL: Inhibition of the growth of WI-38 fibroblasts by benzyloxycarbonyl-Leu-Leu-Tyr diazomethyl ketone: Evidence that cleavage of p53 by a calpain-like protease is necessary for G1 to S-phase transition. Oncogene 14: 255–263, 1997

    PubMed  Google Scholar 

  59. Balcerzak D, Cottin P, Poussard S, Cucuron A, Brustis JJ, Ducastaing A: Calpastatin-modulation of m-calpain activity is required for myoblast fusion. Eur J Cell Biol 75: 247–253, 1998

    PubMed  Google Scholar 

  60. McDonald AD, McDonald JC, Rando RJ, Hughes JM, Weill H: Cohort mortality study of North American industrial sand workers. I. Mortality from lung cancer, silicosis and other causes. Ann Occup Hyg 45: 193–139, 2001

    PubMed  Google Scholar 

  61. Steenland K, Sanderson W: Lung cancer among industrial sand workers exposed to crystalline silica. Am J Epidemiol 153: 695–703, 2001

    Article  PubMed  Google Scholar 

  62. Hessel PA, Gamble JF, Gee JB, Gibbs G, Green FH, Morgan WK, Mossman BT: Silica, silicosis, and lung cancer: A response to a recent working group report. J Occup Environ Med 42: 704–720, 2000

    PubMed  Google Scholar 

  63. Cherry NM, Burgess GL, Turner S, McDonald JC: Crystalline silica and risk of lung cancer in the potteries. Occup Environ Med 55: 779–785, 1998

    PubMed  Google Scholar 

  64. Checkoway H, Franzblau A: Is silicosis required for silica-associated lung cancer? Am J Ind Med 37: 252–259, 2000

    PubMed  Google Scholar 

  65. Bours V, Bentires-Alj M, Hellin AC, Viatour P, Robe P, Delhalle S, Benoit V, Merville MP: Nuclear factor-κB, cancer, and apoptosis. Biochem Pharmacol 60: 1085–1089, 2000

    PubMed  Google Scholar 

  66. Fausto N, Laird AD, Webber EM: Liver regeneration. 2. Role of growth factors and cytokines in hepatic regeneration. FASEB J 9: 1527–1536, 1995

    PubMed  Google Scholar 

  67. Beg AA, Sha WC, Bronson RT, Ghosh S, Baltimore D: Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB. Nature 376: 167–170, 1995

    PubMed  Google Scholar 

  68. Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS Jr: NF-κB antiapoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281: 1680–1683, 1998

    PubMed  Google Scholar 

  69. Stehlik C, de Martin R, Kumabashiri I, Schmid JA, Binder BR, Lipp J: Nuclear factor NF-κB-regulated X-chromosome-linked iap gene expression protects endothelial cells from tumor necrosis factor alphainduced apoptosis. J Exp Med 188: 211–216, 1998

    PubMed  Google Scholar 

  70. Wu MX, Ao Z, Prasad KV, Wu R, Schlossman SF: IEX-1L, an apoptosis inhibitor involved in NF-κB-mediated cell survival. Science 281: 998–1001, 1998

    PubMed  Google Scholar 

  71. Chen F, Demers LM, Vallyathan V, Lu Y, Castranova V, Shi X: Involvement of 5'-flanking κB-like sites within bcl-x gene in silica-induced Bcl-x expression. J Biol Chem 274: 35591–35595, 1999

    PubMed  Google Scholar 

  72. Lee HH, Dadgostar H, Cheng Q, Shu J, Cheng G: NF-κB-mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes. Proc Natl Acad Sci USA 96: 9136–9141, 1999

    PubMed  Google Scholar 

  73. Sarma V, Lin Z, Clark L, Rust BM, Tewari M, Noelle RJ, Dixit VM: Activation of the B-cell surface receptor CD40 induces A20, a novel zinc finger protein that inhibits apoptosis. J Biol Chem 270: 12343–12346, 1995

    Article  PubMed  Google Scholar 

  74. Hinz M, Loser P, Mathas S, Krappmann D, Dorken B, Scheidereit C: Constitutive NF-κB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells. Blood 97: 2798–2807, 2001

    PubMed  Google Scholar 

  75. Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G, Thompson CB: Bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 74: 597–608, 1993

    Article  PubMed  Google Scholar 

  76. Fang W, Weintraub BC, Dunlap B, Garside P, Pape KA, Jenkins MK, Goodnow CC, Mueller DL, Behrens TW: Self-reactive B lymphocytes overexpressing Bcl-xL escape negative selection and are tolerized by clonal anergy and receptor editing. Immunity 9: 35–45, 1998

    PubMed  Google Scholar 

  77. Okada S, Zhang H, Hatano M, Tokuhisa T: A physiologic role of BclxL induced in activated macrophages. J Immunol 160: 2590–2596, 1998

    PubMed  Google Scholar 

  78. Xerri L, Parc P, Brousset P, Schlaifer D, Hassoun J, Reed JC, Krajewski S, Birnbaum D: Predominant expression of the long isoform of Bcl-x [Bcl-xL] in human lymphomas. Br J Haematol 92: 900–906, 1996

    PubMed  Google Scholar 

  79. Bargou RC, Daniel PT, Mapara MY, Bommert K, Wagener C, Kallinich B, Royer HD, Dorken B: Expression of the bcl-2 gene family in normal and malignant breast tissue: Low bax-α expression in tumor cells correlates with resistance towards apoptosis. Int J Cancer 60: 854–859, 1995

    PubMed  Google Scholar 

  80. Hanahan D, Weinberg RA: The hallmarks of cancer. Cell 100: 57–70, 2000

    Article  PubMed  Google Scholar 

  81. Wadgaonkar R, Phelps KM, Haque Z, Williams AJ, Silverman ES, Collins T: CREB-binding protein is a nuclear integrator of nuclear factor-κB and p53 signaling. J Biol Chem 274: 1879–1882, 1999

    Article  PubMed  Google Scholar 

  82. Yang JP, Hori M, Takahashi N, Kawabe T, Kato H, Okamoto T: NF-κB subunit p65 binds to 53BP2 and inhibits cell death induced by 53BP2. Oncogene 18: 5177–5186, 1999

    PubMed  Google Scholar 

  83. Shao J, Fujiwara T, Kadowaki Y, Fukazawa T, Waku T, Itoshima T, Yamatsuji T, Nishizaki M, Roth JA, Tanaka N: Overexpression of the wild-type p53 gene inhibits NF-κB activity and synergizes with aspirin to induce apoptosis in human colon cancer cells. Oncogene 19: 726–736, 2000

    PubMed  Google Scholar 

  84. Joyce D, Bouzahzah B, Fu M, Albanese C, D'Amico M, Steer J, Klein JU, Lee RJ, Segall JE, Westwick JK, Der CJ, Pestell RG: Integration of Rac-dependent regulation of cyclin D1 transcription through a nuclear factor-κB-dependent pathway. J Biol Chem 274: 25245–25249, 1999

    PubMed  Google Scholar 

  85. Guttridge DC, Albanese C, Reuther JY, Pestell RG, Baldwin AS Jr: NF-κB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol Cell Biol 19: 5785–5799, 1999

    PubMed  Google Scholar 

  86. Schwartz SA, Hernandez A, Mark Evers B: The role of NF-κB/IκB proteins in cancer: Implications for novel treatment strategies. Surg Oncol 8: 143–153, 1999

    PubMed  Google Scholar 

  87. Baldwin AS: Control of oncogenesis and cancer therapy resistance by the transcription factor NF-κB. J Clin Invest 107: 241–246, 2001

    PubMed  Google Scholar 

  88. Wang CY, Cusack JC Jr, Liu R, Baldwin AS Jr: Control of inducible chemoresistance: Enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-κB. Nat Med 5: 412–417, 1999

    PubMed  Google Scholar 

  89. Arlt A, Vorndamm J, Breitenbroich M, Folsch UR, Kalthoff H, Schmidt WE, Schafer H: Inhibition of NF-κB sensitizes human pancreatic carcinoma cells to apoptosis induced by etoposide [VP16] or doxorubicin. Oncogene 20: 859–868, 2001

    Article  PubMed  Google Scholar 

  90. Jones DR, Broad RM, Madrid LV, Baldwin AS Jr, Mayo MW: Inhibition of NF-κB sensitizes non-small cell lung cancer cells to chemotherapy-induced apoptosis. Ann Thorac Surg 70: 930–936; discussion 936- 937, 2000

    PubMed  Google Scholar 

  91. Kato T, Duffey DC, Ondrey FG, Dong G, Chen Z, Cook JA, Mitchell JB, Van Waes C: Cisplatin and radiation sensitivity in human head and neck squamous carcinomas are independently modulated by glutathione and transcription factor NF-κB. Head Neck 22: 748–759, 2000

    PubMed  Google Scholar 

  92. Romano MF, Lamberti A, Bisogni R, Tassone P, Pagnini D, Storti G, Del Vecchio L, Turco MC, Venuta S: Enhancement of cytosine arabinoside-induced apoptosis in human myeloblastic leukemia cells by NF-κB/Rel-specific decoy oligodeoxynucleotides. Gene Ther 7: 1234–1237, 2000

    PubMed  Google Scholar 

  93. Cusack JC Jr, Liu R, Baldwin AS Jr: Inducible chemoresistance to 7-ethyl-10-[4-[1-piperidino]-1-piperidino]-carbonyloxycamptothecin [CPT-11] in colorectal cancer cells and a xenograft model is overcome by inhibition of nuclear factor-kB activation. Cancer Res 60: 2323–2330, 2000

    PubMed  Google Scholar 

  94. Sumitomo M, Tachibana M, Ozu C, Asakura H, Murai M, Hayakawa M, Nakamura H, Takayanagi A, Shimizu N: Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IκBα overexpression. Hum Gene Ther 10: 37–47, 1999

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, F., Shi, X. NF-κB, a pivotal transcription factor in silica-induced diseases. Mol Cell Biochem 234, 169–176 (2002). https://doi.org/10.1023/A:1015915000265

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1015915000265

Navigation