Anti-monocyte chemoattractant protein-1 gene therapy attenuates pulmonary fibrosis in mice.
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.
Inoshima
Ichiro
I
Research Inst. for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu Univ., 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Kuwano
Kazuyoshi
K
Hamada
Naoki
N
Hagimoto
Naoki
N
Yoshimi
Michihiro
M
Maeyama
Takashige
T
Takeshita
Akira
A
Kitamoto
Shiro
S
Egashira
Kensuke
K
Hara
Nobuyuki
N
D000818:Animals; D001761:Bleomycin; D018932:Chemokine CCL2 / Q000235:genetics*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000503:physiopathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000628:therapy*; D014162:Transfection
D018932:Chemokine CCL2; D001761:Bleomycin