QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, May 10, 2006, 26(19):5143-5152; doi:10.1523/JNEUROSCI.0737-06.2006

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (14) Citing Articles via Google Scholar Google Scholar Articles by Balabanov, R. Articles by Popko, B. Search for Related Content PubMed PubMed Citation Articles by Balabanov, R. Articles by Popko, B.

 Previous Article  |  Next Article 

Neurobiology of Disease
Suppressor of Cytokine Signaling 1 Expression Protects Oligodendrocytes from the Deleterious Effects of Interferon-

Roumen Balabanov,^1,2 Krystal Strand,^3,4 April Kemper,⁵ Ji Yeon Lee,^1,2 and Brian Popko^1,2

¹Jack Miller Center for Peripheral Neuropathy and ²Department of Neurology, The University of Chicago, Chicago, Illinois 60637, ³Neuroscience Center and ⁴Curriculum for Neurobiology, University of North Carolina, Chapel Hill, North Carolina 27514, and ⁵Department of Pathology, Wake Forest University Baptist Medical Center, Winston Salem, North Carolina 27157

Correspondence should be addressed to Brian Popko, Jack Miller Center for Peripheral Neuropathy, The University of Chicago, Department of Neurology, 5841 South Maryland Avenue, MC2030, Chicago, IL 60637. Email: bpopko{at}uchicago.edu

Interferon- (IFN-) is a pleiotropic cytokine produced by T cells and natural killer cells that has been implicated as a deleterious factor in the immune-mediated demyelinating disorder multiple sclerosis. In vitro, purified developing and mature oligodendrocytes have been shown to die in the presence of IFN- by apoptosis and necrosis, respectively. Moreover, transgenic expression of IFN- in the CNS of mice during development results in tremor, hypomyelination, and oligodendrocyte cell loss, and IFN- expression in adult animals after demyelinating insults inhibits remyelination. To examine the molecular mechanisms of IFN--induced oligodendrocyte injury, we generated a transgenic mouse line [PLP/SOCS1 (proteolipid protein/suppressor of cytokine signaling 1)] that exhibits diminished oligodendrocyte responsiveness to IFN- attributable to the targeted expression of SOCS1 in these cells. We demonstrate that oligodendrocytes in the PLP/SOCS1 transgenic mice are protected against the injurious effect of IFN-. Our data indicate that IFN- exerts a direct deleterious effect on developing oligodendrocytes. The capacity of SOCS1 to inhibit the effects of IFN- suggests a therapeutic approach toward protection of myelinating oligodendrocytes against the harmful effects of inflammation.

Key words: transgenic mice; SOCS1; interferon-; myelin; oligodendrocytes; Stat1

---

Received Feb. 18, 2006; revised April 3, 2006; accepted April 6, 2006.

Correspondence should be addressed to Brian Popko, Jack Miller Center for Peripheral Neuropathy, The University of Chicago, Department of Neurology, 5841 South Maryland Avenue, MC2030, Chicago, IL 60637. Email: bpopko{at}uchicago.edu

This article has been cited by other articles:

				W. Lin, P. E. Kunkler, H. P. Harding, D. Ron, R. P. Kraig, and B. Popko Enhanced Integrated Stress Response Promotes Myelinating Oligodendrocyte Survival in Response to Interferon-{gamma} Am. J. Pathol., November 1, 2008; 173(5): 1508 - 1517. [Abstract] [Full Text] [PDF]

				H. Qin, S. A. Niyongere, S. J. Lee, B. J. Baker, and E. N. Benveniste Expression and Functional Significance of SOCS-1 and SOCS-3 in Astrocytes J. Immunol., September 1, 2008; 181(5): 3167 - 3176. [Abstract] [Full Text] [PDF]

				M. Dubois-Dalcq, A. Williams, C. Stadelmann, B. Stankoff, B. Zalc, and C. Lubetzki From fish to man: understanding endogenous remyelination in central nervous system demyelinating diseases Brain, July 1, 2008; 131(7): 1686 - 1700. [Abstract] [Full Text] [PDF]

				H. Qin, K. L. Roberts, S. A. Niyongere, Y. Cong, C. O. Elson, and E. N. Benveniste Molecular Mechanism of Lipopolysaccharide-Induced SOCS-3 Gene Expression in Macrophages and Microglia J. Immunol., November 1, 2007; 179(9): 5966 - 5976. [Abstract] [Full Text] [PDF]

				R. Balabanov, K. Strand, R. Goswami, E. McMahon, W. Begolka, S. D. Miller, and B. Popko Interferon-{gamma}-Oligodendrocyte Interactions in the Regulation of Experimental Autoimmune Encephalomyelitis J. Neurosci., February 21, 2007; 27(8): 2013 - 2024. [Abstract] [Full Text] [PDF]

				H. Qin, C. A. Wilson, K. L. Roberts, B. J. Baker, X. Zhao, and E. N. Benveniste IL-10 Inhibits Lipopolysaccharide-Induced CD40 Gene Expression through Induction of Suppressor of Cytokine Signaling-3 J. Immunol., December 1, 2006; 177(11): 7761 - 7771. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help