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Inhibition of transcription factor NF-κB in the central nervous system ameliorates autoimmune encephalomyelitis in mice

(2006) NATURE IMMUNOLOGY. 7(9). p.954-961
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Abstract
Activation of transcription factor NF-kappa B in the central nervous system (CNS) has been linked to autoimmune demyelinating disease; however, it remains unclear whether its function is protective or pathogenic. Here we show that CNS-restricted ablation of 'upstream' NF-kappa B activators NEMO or IKK2 but not IKK1 ameliorated disease pathology in a mouse model of multiple sclerosis, suggesting that 'canonical' NF-kappa B activation in cells of the CNS has a mainly pathogenic function in autoimmune demyelinating disease. NF-kappa B inhibition prevented the expression of proinflammatory cytokines, chemokines and the adhesion molecule VCAM-1 from CNS-resident cells. Thus, NF-kappa B-dependent gene expression in non-microglial cells of the CNS provides a permissive proinflammatory milieu that is critical for CNS inflammation and tissue damage in autoimmune demyelinating disease.
Keywords
DEFICIENT MICE, MULTIPLE-SCLEROSIS LESIONS, ANIMAL-MODEL, INFLAMMATION, ASTROCYTES, GENE, EXPRESSION, ACTIVATION, DISEASE, CELL-ADHESION MOLECULE-1

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Chicago
van Loo, Geert, Rossana De Lorenzi, Hauke Schmidt, Marion Huth, Alexander Mildner, Marc Schmidt-Supprian, Hans Lassmann, Marco R Prinz, and Manolis Pasparakis. 2006. “Inhibition of Transcription Factor NF-κB in the Central Nervous System Ameliorates Autoimmune Encephalomyelitis in Mice.” Nature Immunology 7 (9): 954–961.
APA
van Loo, Geert, De Lorenzi, R., Schmidt, H., Huth, M., Mildner, A., Schmidt-Supprian, M., Lassmann, H., et al. (2006). Inhibition of transcription factor NF-κB in the central nervous system ameliorates autoimmune encephalomyelitis in mice. NATURE IMMUNOLOGY, 7(9), 954–961.
Vancouver
1.
van Loo G, De Lorenzi R, Schmidt H, Huth M, Mildner A, Schmidt-Supprian M, et al. Inhibition of transcription factor NF-κB in the central nervous system ameliorates autoimmune encephalomyelitis in mice. NATURE IMMUNOLOGY. 2006;7(9):954–61.
MLA
van Loo, Geert, Rossana De Lorenzi, Hauke Schmidt, et al. “Inhibition of Transcription Factor NF-κB in the Central Nervous System Ameliorates Autoimmune Encephalomyelitis in Mice.” NATURE IMMUNOLOGY 7.9 (2006): 954–961. Print.
@article{1202518,
  abstract     = {Activation of transcription factor NF-kappa B in the central nervous system (CNS) has been linked to autoimmune demyelinating disease; however, it remains unclear whether its function is protective or pathogenic. Here we show that CNS-restricted ablation of 'upstream' NF-kappa B activators NEMO or IKK2 but not IKK1 ameliorated disease pathology in a mouse model of multiple sclerosis, suggesting that 'canonical' NF-kappa B activation in cells of the CNS has a mainly pathogenic function in autoimmune demyelinating disease. NF-kappa B inhibition prevented the expression of proinflammatory cytokines, chemokines and the adhesion molecule VCAM-1 from CNS-resident cells. Thus, NF-kappa B-dependent gene expression in non-microglial cells of the CNS provides a permissive proinflammatory milieu that is critical for CNS inflammation and tissue damage in autoimmune demyelinating disease.},
  author       = {van Loo, Geert and De Lorenzi, Rossana and Schmidt, Hauke and Huth, Marion and Mildner, Alexander and Schmidt-Supprian, Marc and Lassmann, Hans and Prinz, Marco R and Pasparakis, Manolis},
  issn         = {1529-2908},
  journal      = {NATURE IMMUNOLOGY},
  keywords     = {DEFICIENT MICE,MULTIPLE-SCLEROSIS LESIONS,ANIMAL-MODEL,INFLAMMATION,ASTROCYTES,GENE,EXPRESSION,ACTIVATION,DISEASE,CELL-ADHESION MOLECULE-1},
  language     = {eng},
  number       = {9},
  pages        = {954--961},
  title        = {Inhibition of transcription factor NF-κB in the central nervous system ameliorates autoimmune encephalomyelitis in mice},
  url          = {http://dx.doi.org/10.1038/ni1372},
  volume       = {7},
  year         = {2006},
}

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