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Hydrodynamics-based delivery of the viral interleukin-10 gene suppresses experimental crescentic glomerulonephritis in Wistar–Kyoto rats

Gene Therapy volume 10, pages 1297–1310 (2003)Cite this article

Abstract

Gene therapy is expected to revolutionize the treatment of kidney diseases. Viral interleukin (vIL)-10 has a variety of immunomodulatory properties. We examined the applicability of vIL-10 gene transfer to the treatment of rats with crescentic glomerulonephritis, a T helper 1 (Th 1) predominant disease. To produce the disease, Wistar–Kyoto rats were injected with a rabbit polyclonal anti-rat glomerular basement membrane antibody. After 3 h, a large volume of plasmid DNA expressing vIL-10 (pCAGGS-vIL-10) solution was rapidly injected into the tail vein. pCAGGS solution was similarly injected into control rats (pCAGGS rats). We confirmed the presence of vector-derived vIL-10 mainly in the liver and observed high serum vIL-10 levels in pCAGGS-vIL-10-injected rats. Compared with the pCAGGS rats, the pCAGGS-vIL-10 rats showed significant therapeutic effects: reduced frequency of crescent formation, decrease in the number of total cells, macrophages, and CD4+ T cells in the glomeruli, decrease in urine protein, and attenuation of kidney dysfunction. Using quantitative real-time polymerase chain reaction, we also observed that this model was Th1-predominant in the glomeruli and that the ratio of the transcripts of CD4, interferon-γ, tumor necrosis factor-α, and monocyte chemotactic protein-1 to the transcripts of glucose-6-phosphate dehydrogenase in the glomeruli were all significantly lower in the pCAGGS-vIL-10 rats than in the pCAGGS rats. These results demonstrate that pCAGGS-vIL-10 gene transfer by hydrodynamics-based transfection suppresses crescentic glomerulonephritis.

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Acknowledgements

We are grateful to Ms Keiko Yamagiwa and Mr Naofumi Imai of the Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, for technical assistance.

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Authors and Affiliations

  1. Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    N Higuchi, H Maruyama, T Kuroda, S Kameda, N Iino & F Gejyo

  2. Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    H Kawachi

  3. Department of Pathology (I), Akita University School of Medicine, Akita, Japan

    Y Nishikawa

  4. Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    H Hanawa

  5. Department of Surgery, Institute of Medical Science, University of Tokyo, Tokyo, Japan

    H Tahara

  6. Division of Stem Cell Regulation Research, G6, Osaka University Medical School, Suita, Japan

    J Miyazaki

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Higuchi, N., Maruyama, H., Kuroda, T. et al. Hydrodynamics-based delivery of the viral interleukin-10 gene suppresses experimental crescentic glomerulonephritis in Wistar–Kyoto rats. Gene Ther 10, 1297–1310 (2003). https://doi.org/10.1038/sj.gt.3301988

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