Radiation-induced production of PAR-1 and TGF-beta 1 mRNA in lung of C57Bl6 and C3H murine strains and influence of pharmacoprophylaxis by ACE inhibitors
Abstract
Transforming growth factor beta 1 (TGF-beta 1) plays an important role in the development of radiation- and drug-induced organ diseases. Proteinases-activated receptor I (PAR-1) is involved in many pathophysiologic processes after its activation by serine proteases.
The aim of the present study was to determine messenger RNA (mRNA) production of TGF-beta 1 and PAR-1 in the lungs after local irradiation. Mice of C5713L/6 and C3H/J strains with different susceptibility to fibrosis development were exposed to a of 15 Gy.
Non-irradiated mice of both strains were used as negative controls. Control (irradiated) and irradiated angiotensin-converting enzyme (ACE) inhibitor-treated animals were examined simultaneously.
The ACE inhibitor group was given butylaminiperindopril for 9 days after irradiation (15 Gy) at a daily dose of 0.1 or 0.2 mg/kg per rectum. On day 9, all mice were sacrificed, and the production of mRNA TGF-beta 1 and PAR-1 in lung tissue was determined semiquantitatively using reverse transcriptase polymerase chain reaction, and immunohistochemical analysis of PAR-1 expression in pulmonary tissue was performed.
In the fibrosing murine strain C57B1/6, there was an increase in the mRNA TGF-beta 1 and PAR-1 levels in lungs 9 days after irradiation as compared with non-irradiated controls and non-fibrosing murine strain C3H/J. In butylaminiperindopril-treated mice, a decrease in transcript of TGF-beta 1 and PAR-1 was observed.
Thus, PAR-1 is involved in radiation-induced lung fibrosis in correlation with TGF-beta 1 production. Administration of ACET influences PAR-1 and TGF-beta 1 expression.