Amelioration of autoimmune nephritis by imatinib in MRL/lpr mice

Atsushi Sadanaga, Hitoshi Nakashima, Kohsuke Masutani, Katsuhisa Miyake, Sakiko Shimizu, Takashi Igawa, Naonobu Sugiyama, Hiroaki Niiro, Hideki Hirakata, Mine Harada

研究成果: ジャーナルへの寄稿学術誌査読

36 被引用数 (Scopus)


Objective. To examine whether the platelet-derived growth factor (PDGF) receptor antagonist imatinib ameliorates glomerulonephritis in MRL/lpr mice, a condition that is similar to severe lupus nephritis in humans. Methods. Sixteen-week-old MRL/lpr female mice having an advanced stage of glomerulonephritis were divided into 3 groups according to treatment: 1) 50 mg/kg or 2) 10 mg/kg of imatinib (administered orally 4 times a week up to 24 weeks of age) or 3) vehicle solution (untreated group). The histopathologic condition of the kidneys and salivary glands of each mouse as well as the cumulative survival rates, extent of lymphadenopathy and splenomegaly, and serum chemistry and immunologic values were assessed. Results. In mice treated with 50 mg/kg imatinib, neither proliferation of glomerular cells nor crescent formation occurred. A drastic decrease in mesangial matrix was noted. Mice treated with 50 mg/kg imatinib had a prolonged life span compared with mice treated with 10 mg/kg imatinib and untreated mice. Expression of PDGF receptor and transforming growth factor β messenger RNA in the kidneys was significantly reduced in the 50 mg/kg imatinib-treated mice compared with that in the 10 mg/kg imatinib-treated mice (P < 0.05) and the untreated mice (P < 0.01). Intriguingly, lymphadenopathy and salivary gland inflammation were also attenuated in imatinib-treated mice, in a dose-dependent manner. Serum levels of IgG and antidouble-stranded DNA antibodies were also reduced in the imatinib-treated mice. Conclusion. These findings indicate that imatinib has a pleiotropic therapeutic effect, namely, the inhibition of PDGF signaling and immunosuppression, on the glomerulonephritis of MRL/lpr mice, which suggests a potential application of this drug in the treatment of human lupus nephritis.

ジャーナルArthritis and rheumatism
出版ステータス出版済み - 12月 2005

!!!All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • リウマチ学
  • 免疫学
  • 薬理学(医学)


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