PMID- 15064241 OWN - NLM STAT- MEDLINE DCOM- 20040517 LR - 20220227 IS - 1040-0605 (Print) IS - 1040-0605 (Linking) VI - 286 IP - 5 DP - 2004 May TI - Anti-monocyte chemoattractant protein-1 gene therapy attenuates pulmonary fibrosis in mice. PG - L1038-44 AB - 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. FAU - Inoshima, Ichiro AU - Inoshima I AD - Research Inst. for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu Univ., 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. FAU - Kuwano, Kazuyoshi AU - Kuwano K FAU - Hamada, Naoki AU - Hamada N FAU - Hagimoto, Naoki AU - Hagimoto N FAU - Yoshimi, Michihiro AU - Yoshimi M FAU - Maeyama, Takashige AU - Maeyama T FAU - Takeshita, Akira AU - Takeshita A FAU - Kitamoto, Shiro AU - Kitamoto S FAU - Egashira, Kensuke AU - Egashira K FAU - Hara, Nobuyuki AU - Hara N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Physiol Lung Cell Mol Physiol JT - American journal of physiology. Lung cellular and molecular physiology JID - 100901229 RN - 0 (Chemokine CCL2) RN - 11056-06-7 (Bleomycin) SB - IM MH - Animals MH - Bleomycin MH - Chemokine CCL2/*genetics MH - Disease Models, Animal MH - Genetic Therapy/*methods MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Muscle, Skeletal/physiopathology MH - Pulmonary Fibrosis/chemically induced/*therapy MH - Transfection EDAT- 2004/04/06 05:00 MHDA- 2004/05/18 05:00 CRDT- 2004/04/06 05:00 PHST- 2004/04/06 05:00 [pubmed] PHST- 2004/05/18 05:00 [medline] PHST- 2004/04/06 05:00 [entrez] AID - 286/5/L1038 [pii] AID - 10.1152/ajplung.00167.2003 [doi] PST - ppublish SO - Am J Physiol Lung Cell Mol Physiol. 2004 May;286(5):L1038-44. doi: 10.1152/ajplung.00167.2003.