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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1998-7-9
|
| pubmed:abstractText |
CSF-1 and TNF-alpha in the kidney of MRL-Fas(lpr) mice are proximal events that precede and promote autoimmune lupus nephritis, while apoptosis of renal parenchymal cells is a feature of advanced human lupus nephritis. In the MRL-Fas(lpr) kidney, infiltrating T cells that secrete IFN-gamma are a hallmark of disease. To examine the impact of IFN-gamma on renal injury in MRL-Fas(lpr) mice, we constructed a IFN-gamma R-deficient strain. In MRL-Fas(lpr) mice lacking IFN-gamma R, circulating and intrarenal CSF-1 were absent, TNF-alpha was markedly reduced, survival was extended, lymphadenopathy and splenomegaly were prevented, and the kidneys remained protected from destruction. Mesangial cells (MC) that were signaled through the IFN-gamma R induced CSF-1 and TNF-alpha in MRL-Fas(lpr) mice. We detected a large number of apoptotic renal parenchymal cells in advanced nephritis and determined that signaling via the IFN-gamma R induces apoptosis of tubular epithelial cells (TEC), but not MC. By comparison, TNF-alpha induces apoptosis in MC, but not TEC, of the MRL-Fas(lpr) strain. Thus, IFN-gamma is directly and indirectly responsible for apoptosis of TEC and MC in MRL-Fas(lpr) mice, respectively. In conclusion, IFN-gamma R signaling is essential for the initiation (CSF-1), acceleration (CSF-1 and TNF-alpha), and apoptotic destruction of renal parenchymal cells in MRL-Fas(lpr) autoimmune kidney disease.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Colony-Stimulating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interferon,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/interferon gamma receptor
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0022-1767
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
161
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
494-503
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:9647261-Animals,
pubmed-meshheading:9647261-Antigens, CD95,
pubmed-meshheading:9647261-Apoptosis,
pubmed-meshheading:9647261-Autoimmune Diseases,
pubmed-meshheading:9647261-Cell Death,
pubmed-meshheading:9647261-Down-Regulation,
pubmed-meshheading:9647261-Epithelial Cells,
pubmed-meshheading:9647261-Glomerular Mesangium,
pubmed-meshheading:9647261-Interferon-gamma,
pubmed-meshheading:9647261-Kidney,
pubmed-meshheading:9647261-Kidney Function Tests,
pubmed-meshheading:9647261-Kidney Tubules,
pubmed-meshheading:9647261-Lupus Nephritis,
pubmed-meshheading:9647261-Lymphatic Diseases,
pubmed-meshheading:9647261-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:9647261-Mice,
pubmed-meshheading:9647261-Mice, Inbred C57BL,
pubmed-meshheading:9647261-Mice, Inbred MRL lpr,
pubmed-meshheading:9647261-Mice, Inbred Strains,
pubmed-meshheading:9647261-Mice, Knockout,
pubmed-meshheading:9647261-Receptors, Interferon,
pubmed-meshheading:9647261-Signal Transduction,
pubmed-meshheading:9647261-Splenomegaly,
pubmed-meshheading:9647261-Tumor Necrosis Factor-alpha
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
IFN-gamma receptor signaling is essential for the initiation, acceleration, and destruction of autoimmune kidney disease in MRL-Fas(lpr) mice.
|
| pubmed:affiliation |
Renal Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|