NF-κB regulation in the immune system (original) (raw)

• Verma, I. M., Stevenson, J. K., Schwarz, E. M., Van Antwerp, D. & Miyamoto, S. Rel/NF-κB/IκB family: intimate tales of association and dissociation. Genes Dev. 9, 2723–2735 (1995).
  Article CAS PubMed Google Scholar
• Ghosh, S., May, M. J. & Kopp, E. B. NF-κB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 16, 225–260 (1998).
  Article CAS PubMed Google Scholar
• May, M. J. & Ghosh, S. Rel/NF-κB and IκB proteins: an overview. Semin. Cancer Biol. 8, 63–73 (1997).
  Article CAS PubMed Google Scholar
• Silverman, N. & Maniatis, T. NF-κB signaling pathways in mammalian and insect innate immunity. Genes Dev. 15, 2321–2342 (2001).
  Article CAS PubMed Google Scholar
• Gerondakis, S., Grossmann, M., Nakamura, Y., Pohl, T. & Grumont, R. Genetic approaches in mice to understand Rel/NF-κB and IκB function: transgenics and knockouts. Oncogene 18, 6888–6895 (1999).
  Article CAS PubMed Google Scholar
• Dechend, R. et al. The Bcl-3 oncoprotein acts as a bridging factor between NF-κB/Rel and nuclear co-regulators. Oncogene 18, 3316–3323 (1999).
  Article CAS PubMed Google Scholar
• Huxford, T., Huang, D. B., Malek, S. & Ghosh, G. The crystal structure of the IκBα/NF-κB complex reveals mechanisms of NF-κB inactivation. Cell 95, 759–770 (1998).The 2.3 Å crystal structure of IκBα in complex with the NF-κB p50–p65 heterodimer indicates the mechanisms of the inhibitory activity of IκBα.
  Article CAS PubMed Google Scholar
• Birbach, A. et al. Signaling molecules of the NF-κB pathway shuttle constitutively between cytoplasm and nucleus. J. Biol. Chem. 277, 10842–10851 (2002).
  Article CAS PubMed Google Scholar
• Huang, T. T. & Miyamoto, S. Postrepression activation of NF-κB requires the amino-terminal nuclear export signal specific to IκBα. Mol. Cell. Biol. 21, 4737–4747 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Johnson, C., Van Antwerp, D. & Hope, T. J. An N-terminal nuclear export signal is required for the nucleocytoplasmic shuttling of IκBα. EMBO J. 18, 6682–6693 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Huang, T. T., Kudo, N., Yoshida, M. & Miyamoto, S. A nuclear export signal in the N-terminal regulatory domain of IκBα controls cytoplasmic localization of inactive NF-κB/IκBα complexes. Proc. Natl Acad. Sci. USA 97, 1014–1019 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Malek, S., Chen, Y., Huxford, T. & Ghosh, G. IκBβ, but not IκBα, functions as a classical cytoplasmic inhibitor of NF-κB dimers by masking both NF-κB nuclear localization sequences in resting cells. J. Biol. Chem. 276, 45225–45235 (2001).
  Article CAS PubMed Google Scholar
• Lee, S. H. & Hannink, M. Characterization of the nuclear import and export functions of IκBα. J. Biol. Chem. 277, 23358–23366 (2002).
  Article CAS PubMed Google Scholar
• Tam, W. F. & Sen, R. IκB family members function by different mechanisms. J. Biol. Chem. 276, 7701–7704 (2001).
  Article CAS PubMed Google Scholar
• Fenwick, C. et al. A subclass of Ras proteins that regulate the degradation of IκB. Science 287, 869–873 (2000).
  Article CAS PubMed Google Scholar
• Beg, A. A., Sha, W. C., Bronson, R. T. & Baltimore, D. Constitutive NF-κB activation, enhanced granulopoiesis and neonatal lethality in IκBα-deficient mice. Genes Dev. 9, 2736–2746 (1995).
  Article CAS PubMed Google Scholar
• Cheng, J. D., Ryseck, R. P., Attar, R. M., Dambach, D. & Bravo, R. Functional redundancy of the nuclear factor-κB inhibitors IκBα and IκBβ. J. Exp. Med. 188, 1055–1062 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Imler, J. L. & Hoffmann, J. A. Toll and Toll-like proteins: an ancient family of receptors signaling infection. Rev. Immunogenet. 2, 294–304 (2000).
  CAS PubMed Google Scholar
• Akira, S., Takeda, K. & Kaisho, T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nature Immunol. 2, 675–680 (2001).
  Article CAS Google Scholar
• Wang, C. et al. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412, 346–351 (2001).
  Article CAS PubMed Google Scholar
• Kelliher, M. A. et al. The death-domain kinase RIP mediates the TNF-induced NF-κB signal. Immunity 8, 297–303 (1998).
  Article CAS PubMed Google Scholar
• Yang, J. et al. The essential role of MEKK3 in TNF-induced NF-κB activation. Nature Immunol. 2, 620–624 (2001).
  Article CAS Google Scholar
• Arendt, C. W., Albrecht, B., Soos, T. J. & Littman, D. R. Protein kinase Cθ: signaling from the center of the T-cell synapse. Curr. Opin. Immunol. 14, 323–330 (2002).
  Article CAS PubMed Google Scholar
• Sun, Z. et al. PKC-θ is required for TCR-induced NF-κB activation in mature but not immature T lymphocytes. Nature 404, 402–407 (2000).
  Article CAS PubMed Google Scholar
• Ruland, J. et al. Bcl10 is a positive regulator of antigen-receptor-induced activation of NF-κB and neural-tube closure. Cell 104, 33–42 (2001).
  Article CAS PubMed Google Scholar
• McAllister-Lucas, L. M. et al. Bimp1, a MAGUK family member linking protein kinase C activation to Bcl10-mediated NF-κB induction. J. Biol. Chem. 276, 30589–30597 (2001).
  Article CAS PubMed Google Scholar
• Karin, M. & Ben-Neriah, Y. Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu. Rev. Immunol. 18, 621–663 (2000).
  Article CAS PubMed Google Scholar
• Ben-Neriah, Y. Regulatory functions of ubiquitination in the immune system. Nature Immunol. 3, 20–26 (2002).
  Article CAS Google Scholar
• Li, Q., Estepa, G., Memet, S., Israel, A. & Verma, I. M. Complete lack of NF-κB activity in IKK1 and IKK2 double-deficient mice: additional defect in neurulation. Genes Dev. 14, 1729–1733 (2000).The absence of IKK1 and IKK2 completely blocks IκB degradation and NF-κB activation, at least in mouse embryonic fibroblasts, which indicates that IKK1 and IKK2 are key IκB kinases for diverse NF-κB signalling pathways.
  CAS PubMed PubMed Central Google Scholar
• Rudolph, D. et al. Severe liver degeneration and lack of NF-κB activation in NEMO/IKKκ-deficient mice. Genes Dev. 14, 854–862 (2000).
  CAS PubMed PubMed Central Google Scholar
• Li, Q., Van Antwerp, D., Mercurio, F., Lee, K. F. & Verma, I. M. Severe liver degeneration in mice lacking the IκB kinase 2 gene. Science 284, 321–325 (1999).The use of IKK2-deficient mice shows that IKK2 is an important IκB kinase for the degradation of IκB and NF-κB activation.
  Article CAS PubMed Google Scholar
• Hu, Y. et al. IKKα controls formation of the epidermis independently of NF-κB. Nature 410, 710–714 (2001).This study shows that the function of IKK1 in keratinocyte differentiation is independent of its kinase activity and NF-κB activation.
  Article CAS PubMed Google Scholar
• Li, Q. et al. IKK1-deficient mice exhibit abnormal development of skin and skeleton. Genes Dev. 13, 1322–1328 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Sizemore, N., Lerner, N., Dombrowski, N., Sakurai, H. & Stark, G. R. Distinct roles of the IκB kinase α and β subunits in liberating nuclear factor-κB (NF-κB) from IκB and in phosphorylating the p65 subunit of NF-κB. J. Biol. Chem. 277, 3863–3869 (2002).
  Article CAS PubMed Google Scholar
• Cao, Y. et al. IKKα provides an essential link between RANK signaling and cyclin D1 expression during mammary-gland development. Cell 107, 763–775 (2001).
  Article CAS PubMed Google Scholar
• Senftleben, U. et al. Activation by IKKα of a second, evolutionary conserved, NF-κB signaling pathway. Science 293, 1495–1499 (2001).
  Article CAS PubMed Google Scholar
• Xiao, G., Harhaj, E. W. & Sun, S. C. NF-κB-inducing kinase regulates the processing of NF-κB2 p100. Mol. Cell 7, 401–409 (2001).The processing of p100 to generate p52 is inhibited in NIK-deficient cells, which indicates that NIK is necessary for p100 processing.
  Article CAS PubMed Google Scholar
• 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).The authors show that most cases of incontinentia pigmenti are due to mutations of the NEMO gene and that a new genomic rearrangement accounts for 80% of new mutations. As a consequence, NF-κB activation is defective in cells from patients who have incontinentia pigmenti.
  Article CAS PubMed Google Scholar
• Doffinger, R. et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-κB signaling. Nature Genet. 27, 277–285 (2001).
  Article CAS PubMed Google Scholar
• Schmidt-Supprian, M. et al. NEMO/IKKα-deficient mice model incontinentia pigmenti. Mol. Cell 5, 981–992 (2000).
  Article CAS PubMed Google Scholar
• Makris, C. et al. Female mice heterozygous for IKKγ/NEMO deficiencies develop a dermatopathy similar to the human X-linked disorder incontinentia pigmenti. Mol. Cell 5, 969–979 (2000).
  Article CAS PubMed Google Scholar
• Devin, A. et al. The α and β subunits of IκB kinase (IKK) mediate TRAF2-dependent IKK recruitment to tumor-necrosis factor (TNF) receptor 1 in response to TNF. Mol. Cell. Biol. 21, 3986–3994 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Poyet, J. L. et al. Activation of the IκB kinases by RIP via IKKγ/NEMO-mediated oligomerization. J. Biol. Chem. 275, 37966–37977 (2000).
  Article CAS PubMed Google Scholar
• Inohara, N. et al. An induced proximity model for NF-κB activation in the Nod1/RICK and RIP signaling pathways. J. Biol. Chem. 275, 27823–27831 (2000).
  CAS PubMed Google Scholar
• Tarassishin, L. & Horwitz, M. S. Sites on FIP-3 (NEMO/IKKγ) essential for its phosphorylation and NF-κB modulating activity. Biochem. Biophys. Res. Commun. 285, 555–560 (2001).
  Article CAS PubMed Google Scholar
• Carter, R. S., Geyer, B. C., Xie, M., Acevedo-Suarez, C. A. & Ballard, D. W. Persistent activation of NF-κB by the tax transforming protein involves chronic phosphorylation of IκB kinase subunits IKKβ and IKKγ. J. Biol. Chem. 276, 24445–24448 (2001).
  Article CAS PubMed Google Scholar
• Chen, G., Cao, P. & Goeddel, D. V. TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90. Mol. Cell 9, 401–410 (2002).
  Article CAS PubMed Google Scholar
• Peters, R. T. & Maniatis, T. A new family of IKK-related kinases may function as IκB kinase kinases. Biochim. Biophys. Acta 2, M57–M62 (2001).
  Google Scholar
• Kishore, N. et al. IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme, IKK-2. Comparative analysis of rhIKK-i, rhTBK-1 and rhIKK-2. J. Biol. Chem. 277, 13840–13847 (2002).
  Article CAS PubMed Google Scholar
• Bonnard, M. et al. Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-κB-dependent gene transcription. EMBO J. 19, 4976–4985 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Yujiri, T. et al. MEK kinase 1 gene disruption alters cell migration and c-Jun NH2-terminal kinase regulation but does not cause a measurable defect in NF-κB activation. Proc. Natl Acad. Sci. USA 97, 7272–7277 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Xia, Y. et al. MEK kinase 1 is critically required for c-Jun N-terminal kinase activation by proinflammatory stimuli and growth factor-induced cell migration. Proc. Natl Acad. Sci. USA 97, 5243–5248 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Yin, L. et al. Defective lymphotoxin-β receptor-induced NF-κB transcriptional activity in NIK-deficient mice. Science 291, 2162–2165 (2001).
  Article CAS PubMed Google Scholar
• Tojima, Y. et al. NAK is an IκB kinase-activating kinase. Nature 404, 778–782 (2000).
  Article CAS PubMed Google Scholar
• Dumitru, C. D. et al. TNF-α induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway. Cell 103, 1071–1083 (2000).
  Article CAS PubMed Google Scholar
• Leitges, M. et al. Targeted disruption of the ζPKC gene results in the impairment of the NF-κB pathway. Mol. Cell 8, 771–780 (2001).
  Article CAS PubMed Google Scholar
• Zhong, H., Voll, R. E. & Ghosh, S. Phosphorylation of NF-κB p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300. Mol. Cell 1, 661–671 (1998).
  Article CAS PubMed Google Scholar
• Wang, D., Westerheide, S. D., Hanson, J. L. & Baldwin, A. S. Jr. Tumor-necrosis factor-α-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II. J. Biol. Chem. 275, 32592–32597 (2000).
  Article CAS PubMed Google Scholar
• Sakurai, H., Chiba, H., Miyoshi, H., Sugita, T. & Toriumi, W. IκB kinases phosphorylate NF-κB p65 subunit on serine 536 in the transactivation domain. J. Biol. Chem. 274, 30353–30356 (1999).
  Article CAS PubMed Google Scholar
• Hoeflich, K. P. et al. Requirement for glycogen synthase kinase-3β in cell survival and NF-κB activation. Nature 406, 86–90 (2000).
  Article CAS PubMed Google Scholar
• Koul, D., Yao, Y., Abbruzzese, J. L., Yung, W. K. & Reddy, S. A. Tumor suppressor MMAC/PTEN inhibits cytokine-induced NFκB activation without interfering with the IκB degradation pathway. J. Biol. Chem. 276, 11402–11408 (2001).
  Article CAS PubMed Google Scholar
• Eberharter, A. & Becker, P. B. Histone acetylation: a switch between repressive and permissive chromatin: second in review series on chromatin dynamics. EMBO Rep. 3, 224–229 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Lee, S. K., Kim, J. H., Lee, Y. C., Cheong, J. & Lee, J. W. Silencing mediator of retinoic acid and thyroid hormone receptors, as a novel transcriptional corepressor molecule of activating protein-1, nuclear factor-κB and serum response factor. J. Biol. Chem. 275, 12470–12474 (2000).
  Article CAS PubMed Google Scholar
• Ito, K., Barnes, P. J. & Adcock, I. M. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1β-induced histone H4 acetylation on lysines 8 and 12. Mol. Cell Biol. 20, 6891–6903 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Ashburner, B. P., Westerheide, S. D. & Baldwin, A. S. Jr. The p65 (RelA) subunit of NF-κB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression. Mol. Cell. Biol. 21, 7065–7077 (2001).This paper shows that the inhibition of HDAC activity with trichostatin A results in an increase in both basal and induced expression of an integrated NF-κB-dependent reporter gene and that p65 associates directly with HDAC1 and HDAC2.
  Article CAS PubMed PubMed Central Google Scholar
• Chen, L., Fischle, W., Verdin, E. & Greene, W. C. Duration of nuclear NF-κB action regulated by reversible acetylation. Science 293, 1653–1657 (2001).A demonstration that p65 is subject to inducible acetylation and that the acetylation status affects its binding affinity for IκBα. The authors propose that deacetylation of p65 by HDAC3 acts as an intranuclear molecular switch that both controls the duration of the NF-κB transcriptional response and contributes to the replenishment of the depleted cytoplasmic pool of latent NF-κB–IκBα complexes.
  Article CAS Google Scholar
• Zhong, H., May, M. J., Jimi, E. & Ghosh, S. The phosphorylation status of nuclear NF-κB determines its association with CBP/p300 or HDAC-1. Mol. Cell 9, 625–636 (2002).This study shows that induced specific phosphorylation of p65 determines whether it associates with either CBP or HDAC1, which ensures that only p65 that enters the nucleus from cytoplasmic NF-κB–IκB complexes can activate transcription.
  Article CAS PubMed Google Scholar
• Furia, B. et al. Enhancement of nuclear factor-κB acetylation by coactivator p300 and HIV-1 Tat proteins. J. Biol. Chem. 277, 4973–4980 (2002).
  Article CAS PubMed Google Scholar
• Perkins, N. D. The Rel/NF-κB family: friend and foe. Trends Biochem. Sci. 25, 434–440 (2000).
  Article CAS PubMed Google Scholar
• Gerondakis, S., Grumont, R., Rourke, I. & Grossmann, M. The regulation and roles of Rel/NF-κB transcription factors during lymphocyte activation. Curr. Opin. Immunol. 10, 353–359 (1998).
  Article CAS PubMed Google Scholar
• Horwitz, B. H., Scott, M. L., Cherry, S. R., Bronson, R. T. & Baltimore, D. Failure of lymphopoiesis after adoptive transfer of NF-κB-deficient fetal liver cells. Immunity 6, 765–772 (1997).
  Article CAS PubMed Google Scholar
• Senftleben, U., Li, Z. W., Baud, V. & Karin, M. IKKβ is essential for protecting T cells from TNFα-induced apoptosis. Immunity 14, 217–230 (2001).
  Article CAS PubMed Google Scholar
• Boothby, M. R., Mora, A. L., Scherer, D. C., Brockman, J. A. & Ballard, D. W. Perturbation of the T lymphocyte lineage in transgenic mice expressing a constitutive repressor of nuclear factor (NF-κB). J. Exp. Med. 185, 1897–1907 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Caamano, J. & Hunter, C. A. NF-κB family of transcription factors: central regulators of innate and adaptive immune functions. Clin. Microbiol. Rev. 15, 414–429 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Ferreira, V. et al. In vivo inhibition of NF-κB in T-lineage cells leads to a dramatic decrease in cell proliferation and cytokine production and to increased cell apoptosis in response to mitogenic stimuli, but not to abnormal thymopoiesis. J. Immunol. 162, 6442–6450 (1999).
  CAS PubMed Google Scholar
• Mora, A. L., Youn, J., Keegan, A. & Boothby, M. R. NF-κB/Rel participation in the lymphokine-dependent proliferation of T lymphoid cells. J. Immunol. 166, 2218–2227 (2001).
  Article CAS PubMed Google Scholar
• Ouaaz, F., Li, M. & Beg, A. A. A critical role for the RelA subunit of nuclear factor-κB in regulation of multiple immmune-response genes and in Fas-induced cell death. J. Exp. Med. 189, 999–1004 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Kojima, H. et al. An essential role for NF-κB in IL-18-induced IFN-γ expression in KG-1 cells. J. Immunol. 162, 5063–5069 (1999).
  CAS PubMed Google Scholar
• Aronica, M. A. et al. Preferential role for NF-κB/Rel signaling in the type 1 but not type 2 T-cell-dependent immune response in vivo. J. Immunol. 163, 5116–5124 (1999).
  CAS PubMed Google Scholar
• Aune, T. M., Mora, A. L., Kim, S., Boothby, M. R. & Lichtman, A. H. Costimulation reverses the defect in IL-2 but not effector cytokine production by T cells with impaired IκBα degradation. J. Immunol. 162, 5805–5812 (1999).
  CAS PubMed Google Scholar
• Franzoso, G. et al. Requirement for NF-κB in osteoclast and B-cell development. Genes Dev. 11, 3482–3496 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Kaisho, T. et al. IκB kinase α is essential for mature B-cell development and function. J. Exp. Med. 193, 417–426 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Hettmann, T., DiDonato, J., Karin, M. & Leiden, J. M. An essential role for nuclear factor-κB in promoting double-positive thymocyte apoptosis. J. Exp. Med. 189, 145–158 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Baeuerle, P. A. & Baichwal, V. R. NF-κB as a frequent target for immunosuppressive and anti-inflammatory molecules. Adv. Immunol. 65, 111–137 (1997).
  Article CAS PubMed Google Scholar
• Tak, P. P. & Firestein, G. S. NF-κB: a key role in inflammatory diseases. J. Clin. Invest. 107, 7–11 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Yang, L. et al. Essential role of nuclear factor κB in the induction of eosinophilia in allergic airway inflammation. J. Exp. Med. 188, 1739–1750 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Donovan, C. E. et al. NF-κB/Rel transcription factors: c-Rel promotes airway hyperresponsiveness and allergic pulmonary inflammation. J. Immunol. 163, 6827–6833 (1999).
  CAS PubMed Google Scholar
• Bondeson, J., Foxwell, B., Brennan, F. & Feldmann, M. 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 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Miagkov, A. V. et al. NF-κB activation provides the potential link between inflammation and hyperplasia in the arthritic joint. Proc. Natl Acad. Sci. USA 95, 13859–13864 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Yamamoto, Y. & Gaynor, R. B. Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer. J. Clin. Invest. 107, 135–142 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Epinat, J. C. & Gilmore, T. D. Diverse agents act at multiple levels to inhibit Rel/NF-κB signal-transduction pathway. Oncogene 18, 6896–6909 (1999).
  Article CAS PubMed Google Scholar
• Swinney, D. C. et al. A small molecule ubiquitination inhibitor blocks NF-κB-dependent cytokine expression in cells and rats. J. Biol. Chem. 277, 23573–23581 (2002).
  Article CAS PubMed Google Scholar
• Lavon, I. et al. High susceptibility to bacterial infection, but no liver dysfunction, in mice compromised for hepatocyte NF-κB activation. Nature Med. 6, 573–577 (2000).Specific inhibition of NF-κB activity in adult mouse liver does not cause liver apoptosis or dysfunction. However, these mice were unable to clear Listeria monocytogenes from the liver and succumbed to sepsis.
  Article CAS PubMed Google Scholar
• Neurath, M. F., Pettersson, S., 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).These data provide direct evidence for the central importance of p65 in chronic intestinal inflammation and indicate a potential therapeutic use of p65 antisense oligonucleotides as a new molecular approach for the treatment of patients with Crohn's disease.
  Article CAS PubMed Google Scholar
• Aupperle, K. et al. NF-κB regulation by IκB kinase-2 in rheumatoid arthritis synoviocytes. J. Immunol. 166, 2705–2711 (2001).
  Article CAS PubMed Google Scholar
• Campbell, I. K., Gerondakis, S., O'Donnell, K. & Wicks, I. P. Distinct roles for the NF-κB1 (p50) and c-Rel transcription factors in inflammatory arthritis. J. Clin. Invest. 105, 1799–1806 (2000).
  Article CAS PubMed PubMed Central Google Scholar