1. Interferon regulatory factor-1 gene deletion decreases glomerulonephritis in MRL/lpr mice
- Author
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Gary S. Gilkeson, Selen Olgun, Robert M. Gogal, David G. Goodwin, Christopher M. Reilly, S. Ansar Ahmed, Arben Santo, and Jason W. Romesburg
- Subjects
Lipopolysaccharides ,Mice, Inbred MRL lpr ,medicine.medical_specialty ,Immunology ,Lupus nephritis ,Biology ,Kidney ,T-Lymphocytes, Regulatory ,Interferon-gamma ,Mice ,Glomerulonephritis ,Interferon ,Internal medicine ,medicine ,Animals ,Immunology and Allergy ,RNA, Messenger ,IL-2 receptor ,Mesangial cell ,Flow Cytometry ,medicine.disease ,Interleukin-12 ,Lupus Nephritis ,Glomerular Mesangium ,Mice, Inbred C57BL ,STAT1 Transcription Factor ,Endocrinology ,medicine.anatomical_structure ,IRF1 ,Immunoglobulin G ,CD8 ,Interferon Regulatory Factor-1 ,medicine.drug - Abstract
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/lpJfas(lpr) (MRL/lpr) 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-1(-/-) 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 IRF-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/lpr mice.
- Published
- 2006
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