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) |