Journal
JOURNAL OF IMMUNOLOGY
Volume 182, Issue 5, Pages 2628-2640Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0802954
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Funding
- NEI NIH HHS [EY017991, R21 EY017991] Funding Source: Medline
- NINDS NIH HHS [NS051709, R01 NS065479, R01 NS051709, NS46032, R01 NS046032] Funding Source: Medline
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In the CNS, the transcription factor NF-kappa B is a key regulator of inflammation and secondary injury processes. Following trauma protective and detrimental effects. In this study, or disease, the expression of NF-kappa B-dependent genes is activated, leading to both pro we show that transgenic inactivation of astroglial NF-kappa B (glial fibrillary acidic protein-I kappa B alpha-dominant-negative mice) resulted in reduced disease severity and improved functional recovery following experimental autoimmune encephalomyelitis. At the chronic stage of the disease, transgenic mice exhibited an overall higher presence of leukocytes in spinal cord and brain, and a markedly higher percentage of CD8(+)CD122(+) T regulatory cells compared with wild type, which correlated with the timing of clinical recovery. We also observed that expression of proinflammatory genes in both spinal cord and cerebellum was delayed and reduced, whereas the loss of neuronal-specific molecules essential for synaptic transmission was limited compared with wild-type mice. Furthermore, death of retinal ganglion cells in affected retinas was almost abolished, suggesting the activation of neuroprotective mechanisms. Our data indicate that inhibiting NF-kappa B in astrocytes results in neuroprotective effects following experimental autoimmune encephalomyelitis, directly implicating astrocytes in the pathophysiology of this disease. The Journal of Immunology, 2009, 182: 2628-2640.
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