| Proinflammatory orientation of the interleukin 1 system and downstream induction of matrix metalloproteinase 9 in the pathophysiology of human perinatal white matter damage. | |
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MedLine Citation:
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PMID: 20940629 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A preclinical model showed a direct role of the interleukin 1 (IL-1) system in the pathogenesis of perinatal brain damage, but evidence linking these findings to human white matter damage (WMD) requires confirmation in human cases. We analyzed the IL-1β system using immunohistochemistry to characterize the expression of IL-1 receptors (IL-1R1 and IL-1R2), IL-1R antagonist (IL-1Ra), and induction of downstream effectors in 9 human brains with WMD. Interleukin 1β overexpression was associated with IL-1R1 and IL-1R2 immunoreactivity in areas with WMD; immunolabeling for both was detected on astrocytes and microglia/macrophages. There was no immunoreactivity for these receptors in nondamaged white matter in the same brains. Interleukin-1Ra expression was significantly less upregulated than that of IL-1β. This IL-1β/IL-1Ra imbalance was particularly pronounced in the brains of very preterm versus near-term infants. We additionally found overexpression of matrix metalloproteinase 9 (MMP-9) in WMD areas. The MMP-9 colocalized with IL-1β in microglia/macrophages in affected cerebral areas. These data indicate that there is activation and proinflammatory orientation of the IL-1 system with downstream induction of MMP-9 in perinatal WMD. Because both of these mediators are known to be involved in neural cell injury, we infer that IL-1 pathway activation has a deleterious role in the pathophysiology of WMD in human neonates. |
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Authors:
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Sylvie Girard; Guillaume Sébire; Hazim Kadhim |
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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: Journal of neuropathology and experimental neurology Volume: 69 ISSN: 0022-3069 ISO Abbreviation: J. Neuropathol. Exp. Neurol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-27 Completed Date: 2010-11-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985192R Medline TA: J Neuropathol Exp Neurol Country: United States |
Other Details:
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Languages: eng Pagination: 1116-29 Citation Subset: IM |
Affiliation:
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Child Neurology Laboratory, Université de Sherbrooke, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD
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metabolism Antigens, Differentiation, Myelomonocytic / metabolism Apoptosis / physiology Brain Injuries* / enzymology, pathology, physiopathology Female Gene Expression Regulation, Enzymologic / physiology Glial Fibrillary Acidic Protein / metabolism Humans Infant Infant, Newborn Interleukin 1 Receptor Antagonist Protein / metabolism Interleukin-1 / metabolism* Male Matrix Metalloproteinase 9 / metabolism* Nerve Fibers, Myelinated / pathology* Signal Transduction / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Antigens, Differentiation, Myelomonocytic; 0/CD68 antigen, human; 0/Glial Fibrillary Acidic Protein; 0/Interleukin 1 Receptor Antagonist Protein; 0/Interleukin-1; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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