The in vitro synthesis and degradation of prostaglandins during the development of bleomycin-induced pulmonary fibrosis in hamsters.
Subsequent to optimization of conditions for enzyme assay, we examined the in vitro synthesis and degradation of prostaglandins by the lung during the development of bleomycin-induced pulmonary fibrosis in hamsters. It was found that the microsomal protein content on a per lung basis was significantly increased to 144, 129, 134, and 121% of control (2.3 mg protein/lung) at 4, 7, 14 and 21 days post-treatment, respectively. The synthesis of PGD2 was significantly elevated to 10.2, 10.8, and 12.5 nmoles/lung at 7, 21 and 28 days, respectively, as compared to the control value of 5.6 nmoles/lung. Significant increases in PGF2 alpha synthesis from the control value of 3.3 nmoles/lung to 5.2, 8.2 and 5.5 nmoles/lung were found at 4, 7 and 21 days post-treatment, respectively. The synthesis of PGE2 also showed significant increases above the control value of 6.1 nmoles/lung to 10.5, 12.2 and 11.0 nmoles/lung at 7, 21 and 28 days post-treatment, respectively. Similarly, the synthesis of 6-keto-PGF1 alpha was significantly increased to 7.4, 7.5 and 8.6 nmoles/lung at 7, 21 and 28 days post-treatment, respectively, as compared to the control value of 4.4 nmoles/lung. The synthesis of TxB2 was also significantly increased from the control value of 3.9 nmoles/lung to 7.5 and 6.4 nmoles/lung at 7 and 21 days post-treatment, respectively. Accompanying the increased synthesis of prostaglandins in general, the in vitro degradation of PGF2 alpha was significantly increased from the control value of 71.1 nmoles/lung to 173.5, 131.7 and 143.3 nmoles/lung at 2, 4 and 7 days after bleomycin treatment, respectively. We conclude that bleomycin-induced pulmonary fibrosis leads to changes in prostaglandin synthesis and degradation possibly as a result of an accompanying inflammatory response and resident cellular proliferation.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001761:Bleomycin; D006224:Cricetinae; D015237:Dinoprost; D015232:Dinoprostone; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D008861:Microsomes / Q000378:metabolism; D015230:Prostaglandin D2; D011453:Prostaglandins / Q000096:biosynthesis*; D011457:Prostaglandins D / Q000096:biosynthesis; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D011506:Proteins / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D013929:Thromboxane B2 / Q000096:biosynthesis
D011453:Prostaglandins; D011457:Prostaglandins D; D011458:Prostaglandins E; D011460:Prostaglandins F; D011506:Proteins; D001761:Bleomycin; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D015232:Dinoprostone; D015230:Prostaglandin D2