Protective Effect of Urinary Trypsin Inhibitor on the Development of Radiation-Induced Lung Fibrosis in Mice

This study aimed to analyze whether Ulinastatin, a urinary trypsin inhibitor (UTI). inhibits the TGF-beta signaling pathway and lung fibrosis induced by thoracic irradiation in a lung injury mouse model The thoraces of 9-week-old female fibrosis-sensitive C57BL/6 mice were irradiated with a single X-ray dose of 12 Gy or 24 Gy. urn was administrated intraperitoneally at a dose of 200.000 units/kg concurrently with radiation (concurrent UT!) or daily during the post-irradiation period for 8-14 days (post-RT UTI) Mice were sacrificed at 16 weeks alter irradiation to assess the histological grade of lung fibrosis and immunohistochemical TGF-beta expression Survival rates of mice given 24 Gy to the whole lung +/- UTI were also compared Post-RT UTI reduced the score of lung fibrosis in mice, but concurrent UTI had no beneficial effects in irradiated mice. The fibrosis score in post-RT UTI mice was 3 2 +/- 1 0, which was significantly smaller than that of irradiated mice without UTI treatment (RT alone, 6.0 +/- 1.3, p < 0 01) The rates of TGF-beta positive cells in post-RT UTI and the RT alone mice were 0 18 +/- 0 03 and 0.23 +/- 0 04, respectively (p < 0 01) There was a significantly positive correlation between the fibrosis score and the TGF-beta positive rate (R-2 = 0 26, p < 0 01) The survival rate at 30 weeks for post-RT UTI mice was significantly better than that of RT alone mice (33% vs. 10%. p < 0.05) The administration of post-RT UTI suppressed TGF-beta expression and radiation-induced lung fibrosis. which resulted in significant survival prolongation of the irradiated mice