Interferon regulatory factor‐1 gene deletion decreases glomerulonephritis in MRL/lpr mice

European Journal of Immunology - Tập 36 Số 5 - Trang 1296-1308 - 2006
Christopher M. Reilly1,2, Selen Olgun2, David G. Goodwin3, Robert M. Gogal1,2, Arben Santo2, Jason W. Romesburg2, S. Ansar Ahmed3, Gary S. Gilkeson4,5
1Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University
2Via College of Osteopathic Medicine, Blacksburg, VA, USA
3Department of Biomedical Sciences and Pathobiology, Virginia‐Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University
4Department of Medicine, Medical University of South Carolina, Charleston, SC, USA
5Medical Research Service, Ralph H. Johnson VA Medical Center, Charleston, SC, USA

Tóm tắt

AbstractTo 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/lpJfaslpr (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‐α when stimulated with LPS + IFN‐γ. 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.

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European Journal of Immunology

Tập 36 Số 5

1296-1308

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