Source:http://linkedlifedata.com/resource/pubmed/id/12646661
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
2003-3-20
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| pubmed:abstractText |
Autoimmune disease in MRL-Fas(lpr) mice is characterized by fatal nephritis, systemic pathology, and autoantibodies, mimicking human lupus. We previously reported that 1) intrarenal IL-12 elicits nephritis by fostering the accumulation of intrarenal IFN-gamma-secreting T cells, and 2) MRL-Fas(lpr) mice deficient in the IFN-gamma receptor were spared from nephritis. Therefore, we hypothesized that eliminating IL-12 in MRL-Fas(lpr) mice reduces IFN-gamma-secreting cells and thereby prevents systemic pathology. For this purpose, we constructed an IL-12p40-deficient MRL-Fas(lpr)(IL-12(-/-)) strain. We determined that glomerular and interstitial, but not perivascular, renal pathology were decreased in IL-12(-/-) mice vs the wild-type (WT) strain (5 mo of age). Similarly, systemic pathology (lung, lacrimal and salivary glands, skin, and lymphadenopathy) was diminished. The intrarenal accumulation of T cells (CD4(+), CD8(+), CD4(-)CD8(-)B220(+)) and macrophages was dramatically reduced in IL-12(-/-) MRL-Fas(lpr) kidneys. We determined that there were fewer IFN-gamma transcripts (>70%) in the IL-12(-/-) protected kidneys compared with the WT kidneys. Similarly, cells propagated from IL-12(-/-) MRL-Fas(lpr) kidneys generated substantially less IFN-gamma when stimulated with IL-12 and IL-18 compared with those from WT kidneys, and we detected fewer CD8 and B220 T cells producing IFN-gamma in these IL-12(-/-) MRL-Fas(lpr) kidneys. Of note, survival was modestly extended in the IL-12(-/-) MRL-Fas(lpr) mice. While lung and lacrimal and salivary gland pathology remained reduced in moribund IL-12(-/-) MRL-Fas(lpr) mice, renal pathology and IFN-gamma expression were equivalent to those in the WT strain. Thus, we suggest that IL-12 is a therapeutic target for multiple tissues in lupus; however blocking IL-12 alone is not sufficient to confer enduring protection from lupus nephritis.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD45,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/Complement C3,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Isotypes,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Colony-Stimulating Factor
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
170
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3915-25
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:12646661-Animals,
pubmed-meshheading:12646661-Antigens, CD45,
pubmed-meshheading:12646661-Antigens, CD95,
pubmed-meshheading:12646661-CD8-Positive T-Lymphocytes,
pubmed-meshheading:12646661-Complement C3,
pubmed-meshheading:12646661-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:12646661-IgG Deficiency,
pubmed-meshheading:12646661-Immunoglobulin Isotypes,
pubmed-meshheading:12646661-Interferon-gamma,
pubmed-meshheading:12646661-Interleukin-12,
pubmed-meshheading:12646661-Interleukin-18,
pubmed-meshheading:12646661-Interleukin-4,
pubmed-meshheading:12646661-Kidney,
pubmed-meshheading:12646661-Kidney Glomerulus,
pubmed-meshheading:12646661-Kidney Tubules,
pubmed-meshheading:12646661-Lacrimal Apparatus,
pubmed-meshheading:12646661-Leukopenia,
pubmed-meshheading:12646661-Lung,
pubmed-meshheading:12646661-Lupus Nephritis,
pubmed-meshheading:12646661-Lymph Nodes,
pubmed-meshheading:12646661-Lymphatic Diseases,
pubmed-meshheading:12646661-Lymphopenia,
pubmed-meshheading:12646661-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:12646661-Mice,
pubmed-meshheading:12646661-Mice, Inbred C3H,
pubmed-meshheading:12646661-Mice, Inbred C57BL,
pubmed-meshheading:12646661-Mice, Inbred MRL lpr,
pubmed-meshheading:12646661-Mice, Knockout,
pubmed-meshheading:12646661-Salivary Glands,
pubmed-meshheading:12646661-Skin,
pubmed-meshheading:12646661-Survival Rate
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| pubmed:year |
2003
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| pubmed:articleTitle |
IL-12 deficiency in MRL-Fas(lpr) mice delays nephritis and intrarenal IFN-gamma expression, and diminishes systemic pathology.
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| pubmed:affiliation |
Laboratory of Molecular Autoimmune Disease, Renal Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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