Retrovirally introduced prostaglandin D2 synthase suppresses lung injury induced by bleomycin.
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.
Ando
Miyuki
M
Department of Internal Medicine, Kitasato University School of Medicine, Sagamihara-shi, Kanagawa, Japan.
Murakami
Yousuke
Y
Kojima
Fumiaki
F
Endo
Hirahito
H
Kitasato
Hidero
H
Hashimoto
Atsushi
A
Kobayashi
Hirosuke
H
Majima
Masataka
M
Inoue
Matsuhisa
M
Kondo
Hirobumi
H
Kawai
Shinichi
S
Hayashi
Izumi
I
D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D018014:Gene Transfer Techniques; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D054834:Lipocalins; D008168:Lung / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D012190:Retroviridae / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate
D016861:Cyclooxygenase Inhibitors; D006133:Growth Substances; D054834:Lipocalins; D001761:Bleomycin; C037112:9-deoxy-delta-9-prostaglandin D2; D003094:Collagen; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2