| MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. | |
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MedLine Citation:
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PMID: 19952055 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We established microRNA profiles from active and inactive multiple sclerosis lesions. Using laser capture microdissection from multiple sclerosis lesions to pool single cells and in vitro cultures, we assigned differentially expressed microRNA to specific cell types. Astrocytes contained all 10 microRNA that were most strongly upregulated in active multiple sclerosis lesions, including microRNA-155, which is known to modulate immune responses in different ways but so far had not been assigned to central nervous system resident cells. MicroRNA-155 was expressed in human astrocytes in situ, and further induced with cytokines in human astrocytes in vitro. This was confirmed with astrocyte cultures from microRNA-155-|-lacZ mice. We matched microRNA upregulated in phagocytically active multiple sclerosis lesions with downregulated protein coding transcripts. This converged on CD47, which functions as a 'don't eat me' signal inhibiting macrophage activity. Three microRNA upregulated in active multiple sclerosis lesions (microRNA-34a, microRNA-155 and microRNA-326) targeted the 3'-untranslated region of CD47 in reporter assays, with microRNA-155 even at two distinct sites. Our findings suggest that microRNA dysregulated in multiple sclerosis lesions reduce CD47 in brain resident cells, releasing macrophages from inhibitory control, thereby promoting phagocytosis of myelin. This mechanism may have broad implications for microRNA-regulated macrophage activation in inflammatory diseases. |
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Authors:
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Andreas Junker; Markus Krumbholz; Sylvia Eisele; Hema Mohan; Florian Augstein; Robert Bittner; Hans Lassmann; Hartmut Wekerle; Reinhard Hohlfeld; Edgar Meinl |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Brain : a journal of neurology Volume: 132 ISSN: 1460-2156 ISO Abbreviation: Brain Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-16 Completed Date: 2010-02-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372537 Medline TA: Brain Country: England |
Other Details:
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Languages: eng Pagination: 3342-52 Citation Subset: AIM; IM |
Affiliation:
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Institute for Clinical Neuroimmunology, Ludwig Maximilians University, Munich, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Animals Antigens, CD47 / genetics*, metabolism* Astrocytes / metabolism Autoimmunity / genetics, immunology Brain / metabolism*, pathology, physiopathology Cells, Cultured Female Gene Expression Profiling / methods Humans Macrophages / immunology, metabolism Male Mice Mice, Knockout MicroRNAs / analysis, genetics* Microdissection Middle Aged Multiple Sclerosis / genetics*, metabolism*, physiopathology Myelin Sheath / immunology, metabolism Phagocytosis / genetics, immunology Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD47; 0/MicroRNAs |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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