Decreased prostaglandin E2 synthesis by lung fibroblasts isolated from rats with bleomycin-induced lung fibrosis.
In order to clarify the mechanism of pulmonary fibrosis, we examined the functional changes of lung fibroblasts in bleomycin (BLM)-induced pulmonary fibrosis. Lung fibroblastic cells were obtained from rat lungs after an intratracheal treatment of BLM or saline. The spontaneous proliferation of BLM-treated rat fibroblasts (BRF), which was estimated by 3H-TdR incorporation and direct cell counting, was significantly more rapid than that of normal saline-treated rat fibroblasts (NRF). Next, we investigated prostaglandin (PG) E2 synthesis by BRF and NRF, with or without stimulation by interleukin (IL)-1 alpha, and found that PGE2 production by BRF was significantly less than that by NRF. There was no significant difference in cyclooxygenase (COX) activity and COX-2 mRNA level between BRF and NRF, indicating that the change in PGE2 production was independent of COX, a rate-limiting enzyme for the production of PGE2. These results suggest that the proliferation of fibroblasts is down-regulated by PGE2 released from themselves in normal lungs in an autocrine fashion, thus the decreased PGE2 production observed in lung fibroblasts from rats with BLM-induced pulmonary fibrosis may result in the excessive fibroblast proliferation in this disorder. Overall, these findings throw some light on the mechanism of development of BLM-induced pulmonary fibrosis.
Ogushi
F
F
Third Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
Endo
T
T
Tani
K
K
Asada
K
K
Kawano
T
T
Tada
H
H
Maniwa
K
K
Sone
S
S
D000818:Animals; D001761:Bleomycin; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010544:Peroxidases / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D007527:Isoenzymes; D001761:Bleomycin; D010544:Peroxidases; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin