title: Collagen synthesis and degradation in acutely damaged mouse lung tissue following treatment with prednisolone.
abstract: Corticosteroids are widely used to treat patients with acute lung damage. Recent work has shown that the administration of 30 mg/kg prednisolone to mice, twice daily on days 1-5 after the induction of lung damage with butylated hydroxytoluene (BHT), results in the development of a more severe fibrotic lesion [J.P. Kehrer, A.J.P. Klein-Szanto, E. M. B. Sorensen, R. Pearlman and M. H. Rosner, Am. Rev. resp. Dis. 130, 256 (1984)]. In the present study, the rate of collagen synthesis in lung tissue from BHT-saline-treated mice was greater than that in lung tissue from oil-treated controls at all days examined. During prednisolone treatment, the rate of pulmonary collagen synthesis was significantly less in tissue from BHT-prednisolone-treated mice compared to BHT-saline controls. Two days after steroid treatment was stopped (day 7 after BHT), there was a significant increase in the rate of collagen synthesis in lung tissue from BHT-prednisolone-treated mice compared to tissue from both BHT- and oil-treated controls. This increase reached a maximum on day 11 and persisted to day 14 after BHT. The rate of pulmonary non-collagen protein synthesis was inconsistently increased in response to treatments with BHT and/or prednisolone. There was, therefore, a relatively greater increase in the synthesis of collagen. The percentage of total protein synthesis committed to collagen increased from 2% in oil-treated controls to 5% on day 7 after BHT alone and reached a maximum of 7.1% on day 11 in lung tissue from BHT-prednisolone-treated mice. The percentage of newly synthesized collagen that was degraded in lung tissue from BHT-prednisolone-treated mice was significantly lower than BHT-saline on days 7 and 11, and lower than oil-prednisolone on day 14. These results show that collagen synthesis was decreased in BHT-damaged mouse lung tissue during short-term, high-dose steroid therapy. There was, however, an increase in collagen synthesis and a decrease in the degradation of newly synthesized collagen after steroid therapy was stopped. These changes in collagen metabolism may contribute to the steroid-induced enhancement of fibrosis seen in BHT-treated mice.
mesh_terms: D000818:Animals; D002084:Butylated Hydroxytoluene / Q000633:toxicity; D003094:Collagen / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011239:Prednisolone / Q000633:toxicity*; D014176:Protein Biosynthesis
chemical_list: D002084:Butylated Hydroxytoluene; D003094:Collagen; D011239:Prednisolone