| Loss of SHP-1 phosphatase alters cytokine expression in the mouse hindbrain following cochlear ablation. | |
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MedLine Citation:
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PMID: 15341919 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inflammatory cytokines in the central nervous system are largely modulated by glial cells and influence neuronal responses to CNS injury. The protein tyrosine phosphatase SHP-1, an intracellular regulator of many cytokine signaling pathways, has been implicated in mediating the activation of glia. There is a direct correlation between abnormally activated microglia and neuron loss within the SHP-1 deficient motheaten (me/me) mouse auditory brainstem after afferent injury. In order to determine whether loss of SHP-1 creates an aberrant cytokine environment driving the abnormal activation of me/me microglia, the expression of interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) was examined by enzyme-linked immunosorbent assay (ELISA). Normal uninjured me/me mice showed lower IL-10 but higher IL-1beta levels compared to wild-type. Following unilateral cochlear ablation, there is decreased expression of IL-4 and IL-10 in me/me brains compared to wild-type, but IL-1beta is significantly increased. These findings indicate that decreases in anti-inflammatory cytokines, in combination with increased expression of the pro-inflammatory cytokine IL-1beta, may initiate a robust inflammatory reaction within the me/me brain contributing to the neuronal degeneration in the deafferented me/me auditory brainstem. SHP-1 may therefore play a role in limiting CNS inflammation following injury and disease. |
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Authors:
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Jie Zhao; Diana I Lurie |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cytokine Volume: 28 ISSN: 1043-4666 ISO Abbreviation: Cytokine Publication Date: 2004 Oct |
Date Detail:
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Created Date: 2004-09-02 Completed Date: 2005-03-04 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9005353 Medline TA: Cytokine Country: United States |
Other Details:
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Languages: eng Pagination: 1-9 Citation Subset: IM |
Affiliation:
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Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy and Allied Health Sciences, University of Montana, Missoula 59812, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cochlea / surgery* Cytokines / genetics* Functional Laterality Intracellular Signaling Peptides and Proteins Mice Neuroglia / enzymology Protein Tyrosine Phosphatase, Non-Receptor Type 6 Protein Tyrosine Phosphatases / deficiency*, metabolism Rhombencephalon / enzymology*, immunology |
| Grant Support | |
ID/Acronym/Agency:
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DC 02931/DC/NIDCD NIH HHS; P20 RR15583/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Intracellular Signaling Peptides and Proteins; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 6; EC 3.1.3.48/Protein Tyrosine Phosphatases; EC 3.1.3.48/Ptpn6 protein, mouse |
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