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

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Abstract

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.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume286
Issue number5 30-5
DOIs
Publication statusPublished - May 1 2004

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Pulmonary Fibrosis
Chemokine CCL2
Genetic Therapy
Mutant Proteins
Bleomycin
DNA Damage
Viral Antibodies
Apoptosis
Neutralizing Antibodies
Chemokines
Genes
Transfection
Virulence
Pneumonia
Skeletal Muscle
Fibrosis
Therapeutics

All Science Journal Classification (ASJC) codes

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

Cite this

Anti-monocyte chemoattractant protein-1 gene therapy attenuates pulmonary fibrosis in mice. / Inoshima, Ichiro; Kuwano, Kazuyoshi; Hamada, Naoki; Hagimoto, Naoki; Yoshimi, Michihiro; Maeyama, Takashige; Takeshita, Akira; Kitamoto, Shiro; Egashira, Kensuke; Hara, Nobuyuki.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 286, No. 5 30-5, 01.05.2004.

Research output: Contribution to journalArticle

Inoshima, Ichiro ; Kuwano, Kazuyoshi ; Hamada, Naoki ; Hagimoto, Naoki ; Yoshimi, Michihiro ; Maeyama, Takashige ; Takeshita, Akira ; Kitamoto, Shiro ; Egashira, Kensuke ; Hara, Nobuyuki. / Anti-monocyte chemoattractant protein-1 gene therapy attenuates pulmonary fibrosis in mice. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2004 ; Vol. 286, No. 5 30-5.
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