| Increased expression of pro-inflammatory cytokines and lack of up-regulation of anti-inflammatory cytokines in early distemper CNS lesions. | |
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MedLine Citation:
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PMID: 11960638 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To investigate the pathogenesis of early lesions in canine distemper virus (CDV) leukoencephalomyelitis, the expressions of pro- and anti-inflammatory cytokines such as interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and transforming growth factor (TGF)-beta and the housekeeping genes beta-actin and GAPDH were studied using semi-quantitative RT-PCR. Relative cytokine values were related to the degree of CDV infection, MHC class II expression and infiltration of CD4-, CD8- and CD3epsilon-positive lymphocytes. Actin up-regulation, in contrast to GAPDH, was influenced by CDV infection and therefore could not be used as an internal standard to study cytokine expression. In early CDV infection of the cerebellum, either no detectable lesions or mild infiltration of CD8 positive cells or demyelination and up-regulation of MHC class II antigen were observed. IL-6, -8, -12 and TNF-alpha transcripts were found in 94%, 94%, 78% and 56% of distemper dogs, respectively, compared to 17%, 33%, 0% and 0% in controls, whereas IL-1beta, -2 and IFN-gamma were not detectable in any of the studied cerebella. Conversely, IL-10 and TGF-beta transcripts were present in 83% and 100% of the investigated cerebella of distemper dogs and controls. Relative RT-PCR results, expressed as %GAPDH, revealed a significant up-regulation of IL-6, -8, -12 and TNF-alpha mRNA in distemper dogs; whereas IL-10 and TGF-beta showed only a weak and not significantly increased expression following infection. Relative pro-inflammatory cytokine expression values were highest following CDV infection, indicating that the virus itself directly triggered the up-regulation of the pro-inflammatory cytokines. Succeeding changes, such as lymphocyte infiltration, MHC class II up-regulation and demyelination resulted only in a minor additional increase in cytokine expression, implying a secondary or by-stander mechanism of cytokine activation by these changes. Disease initiation and progression in early distemper leukoencephalomyelitis seemed to be due to a lacking or inappropriate response of the anti-inflammatory cytokines in the presence of a vigorous up-regulation of pro-inflammatory cytokines. |
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Authors:
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Stefanie Markus; K Failing; Wolfgang Baumgärtner |
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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 neuroimmunology Volume: 125 ISSN: 0165-5728 ISO Abbreviation: J. Neuroimmunol. Publication Date: 2002 Apr |
Date Detail:
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Created Date: 2002-04-18 Completed Date: 2002-05-31 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8109498 Medline TA: J Neuroimmunol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 30-41 Citation Subset: IM |
Affiliation:
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Institut für Veterinär-Pathologie, Justus-Liebig-Universität Giessen, Frankfurter Str. 96, 35392 Giessen, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cytokines / genetics* Disease Progression Distemper / etiology, immunology*, pathology Distemper Virus, Canine / genetics*, isolation & purification Dogs Gene Expression / immunology Glyceraldehyde-3-Phosphate Dehydrogenases / genetics Interleukin-12 / genetics Interleukin-12 Subunit p40 Interleukin-6 / genetics Interleukin-8 / genetics Protein Subunits RNA, Messenger / analysis RNA, Viral / analysis Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha / genetics Up-Regulation / immunology |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Interleukin-12 Subunit p40; 0/Interleukin-6; 0/Interleukin-8; 0/Protein Subunits; 0/RNA, Messenger; 0/RNA, Viral; 0/Tumor Necrosis Factor-alpha; 187348-17-0/Interleukin-12; EC 1.2.1.-/Glyceraldehyde-3-Phosphate Dehydrogenases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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