Decreased prostaglandin E2 synthesis by lung fibroblasts isolated from rats with bleomycin-induced lung fibrosis

• Published in: International journal of experimental pathology 1999-01, Vol.80 (1), p.41-49
• Main Authors: OGUSHI, FUMITAKA, ENDO, TAKESHI, TANI, KENJI, ASADA, KANJI, KAWANO, TETSUYA, TADA, HIROYA, MANIWA, KOJI, SONE, SABURO
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bleomycin; bleomycin fibrosis; Cell Culture Techniques; Cell Division - drug effects; Cyclooxygenase 2; Dinoprostone - biosynthesis; Dinoprostone - pharmacology; Drug toxicity and drugs side effects treatment; fibroblast; Fibroblasts - metabolism; Immunoenzyme Techniques; Indomethacin - pharmacology; Isoenzymes - metabolism; Lung - metabolism; Lung - pathology; Male; Medical sciences; Original; Peroxidases - metabolism; Pharmacology. Drug treatments; prostaglandin E2; Prostaglandin-Endoperoxide Synthases - metabolism; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Rats; Rats, Wistar; Toxicity: respiratory system, ent, stomatology
• ISSN: 0959-9673; 1365-2613
• DOI: 10.1046/j.1365-2613.1999.00096.x

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)‐1α, 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.