Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 36, Issue 5, Pages 1296-1308Publisher
WILEY
DOI: 10.1002/eji.200535245
Keywords
interferon regulatory; factor-1; kidney; lupus; mouse; MRL
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Funding
- NIAMS NIH HHS [AR0493190-03] Funding Source: Medline
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To investigate the role of interferon regulatory factor-1 (IRF-1) in the development of lupus nephritis, IRF-1(-/-) genotype mice were bred onto the MRL/1pJfas(1pr) (MRL/1pr) background. We examined kidney mesangial cell function and disease progression. Endpoints evaluated included inflammatory mediators, autoantibody production, immune complex deposition, renal pathology, T cell subset analysis, and duration of survival. Mesangial cells cultured from IRF-1(-/-) mice produced significantly lower levels of nitric oxide and IL-12 but not TNF-alpha when stimulated with LPS + IFN-gamma. IRF-/- mice showed less aggravated dermatitis compared to the wild-type mice. Anti-double-stranded DNA production and proteinuria were significantly decreased in IRF-1(-/-) mice compared to lRF-1(+/+) mice. IgG and C3 deposition as well as glomerulonephritis were decreased in IRF-1(-/-) mice at 26 wk of age compared to the IRF-1(+/+) mice. Splenic CD4(-)CD8(-)CD44(+) T cells were decreased while CD4(+)CD25(+) T cells were increased in the IRF-1(-/-) mice when compared to IRF-1(+/+) mice. Survival rates (ED50) were 22 wk for IRF-1(+/+) mice and 45 wk for IRF-1(-/-) mice. These findings suggest an important role of IRF-1 in mediating renal disease in MRL/1pr mice.
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