Journal article
Transgenic Inhibition of Astroglial NF-kappa B Improves Functional Outcome in Experimental Autoimmune Encephalomyelitis by Suppressing Chronic Central Nervous System Inflammation
The Journal of immunology (1950), Vol.182(5), pp.2628-2640
01 Mar 2009
PMID: 19234157
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- Transgenic Inhibition of Astroglial NF-kappa B Improves Functional Outcome in Experimental Autoimmune Encephalomyelitis by Suppressing Chronic Central Nervous System Inflammation
- Creators
- Roberta Brambilla - University of MiamiTrikaldarshi Persaud - University of MiamiXianchen Hu - University of Alabama at BirminghamShaffiat Karmally - University of MiamiValery I. Shestopalov - University of MiamiGalina Dvoriantchikova - University of MiamiDmitry Ivanov - University of MiamiLubov Nathanson - University of MiamiScott R. Barnum - University of Alabama at BirminghamJohn R. Bethea - University of Miami
- Publication Details
- The Journal of immunology (1950), Vol.182(5), pp.2628-2640
- Publisher
- American Association of Immunologists
- Number of pages
- 13
- Grant note
- R21EY017991 / NATIONAL EYE INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) R01NS051709 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) R21 EY017991; EY017991 / NEI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) NS051709; R01 NS046032; R01 NS051709; R01 NS065479; NS46032 / NINDS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Identifiers
- 991020100070104721
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- Web of Science research areas
- Immunology