Source:http://linkedlifedata.com/resource/pubmed/id/20952683
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2010-11-4
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| pubmed:abstractText |
The etiology of salivary gland injury in primary Sjögren's disease is not well understood. We have previously described a mouse model of Sjögren's disease, IL-14? transgenic (IL14?TG) mice, which reproduces many of the features of the human disease. We now demonstrate a critical role for lymphotoxin ? (LTA) in the pathogenesis of Sjögren's disease in IL14?TG mice. IL14?TG mice express LTA mRNA in their salivary glands and spleen and produce soluble LTA protein in their salivary secretions. When IL14?TG mice were crossed with LTA(-/-) mice, the IL14?TG.LTA(-/-) mice retained normal salivary gland secretions and did not develop either lymphocytic infiltration of their salivary glands or secondary lymphomas. However, both IL14?TG and IL14?TG.LTA(-/-) mice produced similar amounts of IFN-? and had similar deposition of autoantibodies in their salivary glands. Both IL14? and IL14?/LTA(-/-) mice had similar B cell responses to T-dependent and T-independent Ags, L-selectin expression, and expression of RelA, RelB, and NF-?B2 in their spleens. These studies suggest that LTA plays a critical role in the local rather than systemic inflammatory process of Sjögren's disease. Furthermore, local production of soluble LTA in the salivary glands of IL14?TG mice is necessary for the development of overt Sjögren's disease. Autoantibody deposition alone is not sufficient to produce salivary gland dysfunction. We also demonstrate that LTA is increased in the salivary gland secretions and sera of patients with Sjögren's disease, further strengthening the biological relevance of the IL14?TG model to understanding the pathogenesis of human disease.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
1550-6606
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
15
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| pubmed:volume |
185
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
6355-63
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| pubmed:meshHeading |
pubmed-meshheading:20952683-Animals,
pubmed-meshheading:20952683-Autoantibodies,
pubmed-meshheading:20952683-Blotting, Western,
pubmed-meshheading:20952683-Cell Separation,
pubmed-meshheading:20952683-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:20952683-Female,
pubmed-meshheading:20952683-Flow Cytometry,
pubmed-meshheading:20952683-Fluorescent Antibody Technique,
pubmed-meshheading:20952683-Humans,
pubmed-meshheading:20952683-Interleukins,
pubmed-meshheading:20952683-Lymphotoxin-alpha,
pubmed-meshheading:20952683-Male,
pubmed-meshheading:20952683-Mice,
pubmed-meshheading:20952683-Mice, Inbred C57BL,
pubmed-meshheading:20952683-Mice, Knockout,
pubmed-meshheading:20952683-Mice, Transgenic,
pubmed-meshheading:20952683-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20952683-Saliva,
pubmed-meshheading:20952683-Salivary Glands,
pubmed-meshheading:20952683-Sjogren's Syndrome,
pubmed-meshheading:20952683-Spleen
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| pubmed:year |
2010
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| pubmed:articleTitle |
A role for lymphotoxin in primary Sjogren's disease.
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| pubmed:affiliation |
Division of Allergy, Immunology and Rheumatology, Department of Medicine, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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