RRC ID 42803
Author Muraoka M, Hasegawa H, Kohno M, Inoue A, Miyazaki T, Terada M, Nose M, Yasukawa M.
Title IK cytokine ameliorates the progression of lupus nephritis in MRL/lpr mice.
Journal Arthritis Rheum
Abstract OBJECTIVE:IK cytokine has been isolated as a factor that inhibits interferon-gamma (IFNgamma)-induced expression of class II major histocompatibility complex (MHC) antigens. Aberrant expression of class II MHC antigens has reportedly been recognized in the target organs of autoimmune diseases and been associated with disease activity. In this study, we investigated whether IK cytokine can ameliorate the progression of lupus nephritis in MRL/lpr mice.
METHODS:A truncated IK analog was prepared and transfected into a nonmetastatic fibroblastoid cell line, and then injected subcutaneously into MRL/lpr mice at ages 8 weeks (before the onset of lupus nephritis) and 12 weeks (at the early stage of the disease).
RESULTS:An IK cytokine, when it was translated from methionine at position 316, acted as a secretory protein. This truncated IK cytokine (tIK) reduced IFNgamma-induced class II MHC expression in various cells through decreased expression of class II MHC transcription activator. Treatment of MRL/lpr mice with tIK significantly reduced renal damage as compared with control mice. A significant decrease in macrophage and T cell infiltration was found in the kidneys of tIK-treated mice, resulting in decreased production of IFNgamma and interleukin-2. Mice treated with tIK also showed significant reduction of anti-DNA antibodies and circulating immune complexes. A specific reduction of class II MHC expression was observed on B cells and monocytes as well as in the kidney.
CONCLUSION:We prepared a potent IK analog and demonstrated its ability to ameliorate the progression of lupus nephritis. This agent may therefore provide a new therapeutic approach for lupus nephritis.
Volume 54(11)
Pages 3591-600
Published 2006-11
DOI 10.1002/art.22172
PMID 17075801
MeSH Animals Antibodies, Antinuclear / blood Bone Marrow Cells / cytology Bone Marrow Cells / immunology Cell Line Cytokines / genetics* Cytokines / immunology* Cytokines / metabolism Disease Progression Gene Expression / immunology Genetic Therapy / methods* Histocompatibility Antigens Class II / genetics Interferon-gamma / blood Interferon-gamma / pharmacology Interleukin-2 / blood Kidney / blood supply Kidney / pathology Kidney / physiology Lupus Nephritis / immunology* Lupus Nephritis / pathology Lupus Nephritis / therapy* Macrophages / cytology Macrophages / drug effects Macrophages / physiology Mice Mice, Inbred MRL lpr Spleen / physiology Transfection Vasculitis / immunology Vasculitis / pathology Vasculitis / therapy
Times Cited 19
Human and Animal Cells