Anti-monocyte chemoattractant protein-1 gene therapy attenuates pulmonary fibrosis in mice

Ichiro Inoshima, Kazuyoshi Kuwano, Naoki Hamada, Naoki Hagimoto, Michihiro Yoshimi, Takashige Maeyama, Akira Takeshita, Shiro Kitamoto, Kensuke Egashira, Nobuyuki Hara

研究成果: ジャーナルへの寄稿記事

100 引用 (Scopus)

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Monocyte chemoattractant protein-1 (MCP-1) is a proinflammatory chemokine and may play an important role in the development of pulmonary fibrosis. We examined a new therapeutic strategy that comprises the transfection of the mutant MCP-1 gene into skeletal muscles as a biofactory for anti-MCP-1 therapy against bleomycin-induced pulmonary fibrosis in mice. Overexpression of the mutant MCP-1 gene at 10-14 days after intratracheal instillation of bleomycin resulted in decreased DNA damage, apoptosis, and pulmonary fibrosis at 14 days. However, overexpression of the mutant MCP-1 at 0-4 days after bleomycin instillation did not result in decreased pathological grade, DNA damage, or apoptosis at 7 and 14 days. Because, in this model, inflammatory cell infiltration begins at 3 days and is followed by interstitial fibrosis, it is likely that MCP-1 has an important role to play in the development of fibrogenesis but not in the development of early lung inflammation. This method does not require the use of viral vector or neutralizing antibody, and, as such, it is possible to avoid problems regarding the pathogenicity of the viral vector or immunocomplex. This new strategy may be a beneficial method of treating pulmonary fibrosis from the viewpoint of clinical application.

元の言語英語
ページ(範囲)L1038-L1044
ジャーナルAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
286
発行部数5 30-5
DOI
出版物ステータス出版済み - 5 1 2004

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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