IK cytokine ameliorates the progression of lupus nephritis in MRL/lpr mice

Masatake Muraoka, Hitoshi Hasegawa, Masashi Kohno, Atsushi Inoue, Tatsuhiko Miyazaki, Miho Terada, Masato Nose, Masaki Yasukawa

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Objective. IK cytokine has been isolated as a factor that inhibits Interferon-γ (IFNγ)-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 MKL/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 IFNγ-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 IFNγ 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.

Original languageEnglish
Pages (from-to)3591-3600
Number of pages10
JournalArthritis and Rheumatism
Volume54
Issue number11
DOIs
Publication statusPublished - 2006 Nov

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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