RRC ID 41856
著者 Ando M, Murakami Y, Kojima F, Endo H, Kitasato H, Hashimoto A, Kobayashi H, Majima M, Inoue M, Kondo H, Kawai S, Hayashi I.
タイトル Retrovirally introduced prostaglandin D2 synthase suppresses lung injury induced by bleomycin.
ジャーナル Am J Respir Cell Mol Biol
Abstract Hematopoietic prostaglandin D synthase (PGDS) is a key enzyme to produce prostaglandin (PG) D and J series. These PGs are involved in inflammation and immune system. The PGDS complementary DNA (cDNA)-expressing retrovirally transfected fibroblasts were introduced in vivo, and effect of the expression on lung injury induced by bleomycin was investigated in mice. Intravenous injection of PGDS cDNA-expressing fibroblasts significantly reduced lung edema, leukocyte infiltration in bronchoalveolar lavage (BAL) fluid, and pulmonary collagen content at 4 wk after instillation of bleomycin. Survival rate in mice instilled with the PGDS-expressing fibroblasts was higher than that in mice that received the mock transfection. Administration of 15-deoxy-Delta 12,14-PGJ2, which is a nonenzymatic metabolite of PGD2, also attenuated the lung injury, suggesting mediation of PGs produced by PGDS for the attenuation. Introduction of PGDS cDNA-expressing fibroblasts suppressed expression of basic fibroblast growth factor, connective tissue growth factor, and collagen messenger RNAs in the lungs, as well as the levels of total proteins and hemoglobin in BAL fluid. These data suggest that the suppressive effect of PGDS on the lung injury could be partly mediated by edema formation and inhibition of genes involved in the fibrotic change.
巻・号 28(5)
ページ 582-91
公開日 2003-5-1
DOI 10.1165/rcmb.2002-0162OC
PII 28/5/582
PMID 12707014
MeSH Animals Bleomycin / toxicity* Body Weight Bronchoalveolar Lavage Fluid / chemistry Bronchoalveolar Lavage Fluid / cytology Cells, Cultured Collagen / genetics Collagen / metabolism Cyclooxygenase Inhibitors / metabolism Fibroblasts / cytology Fibroblasts / metabolism Gene Transfer Techniques Growth Substances / genetics Growth Substances / metabolism Humans In Situ Hybridization Intramolecular Oxidoreductases / genetics Intramolecular Oxidoreductases / metabolism* Lipocalins Lung / pathology* Male Mice Mice, Inbred C57BL Prostaglandin D2 / administration & dosage Prostaglandin D2 / analogs & derivatives* Prostaglandin D2 / chemistry Retroviridae / genetics* Retroviridae / metabolism Survival Rate
IF 5.373
引用数 33
WOS 分野 RESPIRATORY SYSTEM BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 C57BL/6J-emb(RCB1312)