| Elevated levels of IFNγ and LIGHT in the spinal cord of patients with sporadic amyotrophic lateral sclerosis. | |
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MedLine Citation:
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PMID: 22221541 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Background: Amyotrophic lateral sclerosis (ALS) is a paralytic and fatal neurodegenerative disorder caused by the gradual loss of both upper and lower motoneurons. There is compelling evidence from ALS experimental models that neuroinflammation actively contributes to motoneuron damage. We recently proposed that interferon gamma (IFNγ), a potent proinflammatory cytokine, induces motoneuron death by eliciting the activation of the lymphotoxin beta receptor (LT-βR) through its ligand LIGHT. Here, we explore the pertinence of this non-cell-autonomous mechanism in human ALS. Methods: The levels and expression pattern of IFNγ, LIGHT, and LT-βR were investigated by Western blot and immunohistochemical analysis in spinal cord of patients with sporadic ALS. Results: We observed significant increased levels of IFNγ in human ALS spinal cords compared to control cases. We found that large ventral horn neurons as well as glial cells were immunoreactive for IFNγ in sporadic ALS spinal cord. We further observed that LIGHT and LT-βR were expressed mainly by motoneurons in both ALS and control cases, and while LT-βR levels remained constant between ALS and control cases, LIGHT levels were increased in human ALS spinal cords. Conclusion: These findings in sporadic ALS cases, which are consistent with the observation made in ALS experimental models, propose that the IFNγ-triggered LIGHT/LT-βR-mediated death pathway may contribute to human ALS pathogenesis. |
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Authors:
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J Aebischer; A Moumen; V Sazdovitch; D Seilhean; V Meininger; C Raoul |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-4 |
Journal Detail:
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Title: European journal of neurology : the official journal of the European Federation of Neurological Societies Volume: - ISSN: 1468-1331 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9506311 Medline TA: Eur J Neurol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 The Author(s). European Journal of Neurology © 2012 EFNS. |
Affiliation:
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Inserm-Avenir Team, the Mediterranean Institute of Neurobiology, INMED, Marseille Université de la Méditerranée, UMR S901 Aix-Marseille 2, Marseille Département de Neuropathologie, UPMC Université Paris, Assistance Publique Hôpitaux de Paris, Hopital de la Pitié-Salpêtrière, Paris Département des maladies du système nerveux, Hôpital de la Salpêtrière, AP-HP, Paris, France. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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