IRF-1 signaling in central nervous system glial cells regulates inflammatory demyelination.

Abstract

The present study provides evidence that interferon regulatory factor 1 (IRF-1) signaling in glial cells is involved in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Using a bone marrow chimera model of EAE, we demonstrated that CNS IRF-1 regulates inflammatory demyelination and disease severity independently of the peripheral immune cells. In addition, we identified Caspase 1, a pro-inflammatory and pro-apoptotic molecule, as an important transcriptional target of IRF-1. The findings of our study indicate that IRF-1 signaling in glial cells serves as a final common pathway of inflammatory demyelination and may have important clinical implications in MS.

• Authors: Zhihua Ren, Yan Wang, David Liebenson, Thomas Liggett, Rajendra Goswami, Dusan Stefoski, Roumen Balabanov
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 233 Issue 1-2 Pg. 147-59 (Apr 2011) ISSN: 1872-8421 [Electronic] Netherlands
• PMID: 21257209 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Interferon Regulatory Factor-1

Topics

• Animals
• Cells, Cultured
• Demyelinating Autoimmune Diseases, CNS (immunology, metabolism, pathology)
• Disease Models, Animal
• Encephalomyelitis, Autoimmune, Experimental (immunology, metabolism, physiopathology)
• Fatal Outcome
• Female
• Humans
• Immunomodulation (drug effects, immunology)
• Interferon Regulatory Factor-1 (deficiency, genetics, physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Middle Aged
• Multiple Sclerosis (immunology, metabolism, physiopathology)
• Neuroglia (immunology, metabolism, pathology)
• Signal Transduction (drug effects, immunology)