5-Azacytidine inhibits the lpr gene-induced lymphadenopathy and acceleration of lupus-like syndrome in MRL/MpJ-lpr/lpr mice.
MRL/MpJ-lpr/lpr mice spontaneously develop a lupus-like autoimmune disorder characterized by massive proliferation of T cells and rapidly fatal immune complex glomerulonephritis. We evaluated the therapeutic effect of 5-azacytidine (5AC), a cytidine analogue known as an inhibitor of DNA methylation, in MRL/MpJ-lpr/lpr mice. Intraperitoneal injection of 5AC (50 micrograms, twice a week) starting from 6 weeks of age retarded the development of lymphadenopathy and autoimmune syndrome. Its beneficial effects included: (a) increased life-span, (b) diminution of lymphadenopathy and splenomegaly, (c) reduction in circulating levels of autoantibodies such as anti-DNA and rheumatoid factors, and (d) suppression of lupus glomerulonephritis. However, similar treatment in BALB/c mice did not affect the development of IgG anti-human IgG antibody responses. These results suggest that the protective effect of 5AC is related to the inhibition of the lpr gene-induced T cell proliferation, thereby suppressing the autoimmunity-accelerating effect mediated by the lpr gene.
Department of Pathology, Faculty of Medicine, Kyoto University.
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H
Yoshida
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Yoshida
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R
Merino
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Shibata
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Izui
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000235:genetics / Q000401:mortality / Q000517:prevention & control*; D001374:Azacitidine / Q000627:therapeutic use*; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008181:Lupus Nephritis / Q000517:prevention & control*; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000401:mortality / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D001374:Azacitidine