Our group has previously shown that PDE3 inhibitor / 4 reduces the migration of arterial smooth GDC-0980 muscle cells in vitro and pulmonary reverse the pulmonary vascular Remodeling in vivo. PDE4 inhibitor cilomilast has also been shown to inhibit the release and activation of MMP-1 and MMP 9 from lung fibroblasts, which are known to be involved in the progression of PF. Moreover cilomilast and other PDE4 inhibitors have been shown to inhibit the release of TNF and TGF lung and the influx of neutrophils in vivo. After all,, the treatment of chronic experimental colitis with PDE4 inhibitor rolipram to collagen decreases and lodgment TNF and TGF-content in the tissue. In the present study, we hypothesized that PDE4 inhibitors k Able to modulate the inflammatory response in a time and tissue remodeling are.
The purpose of this study was to examine the effects of the selective PDE4 inhibitor on various aspects of the experimental PF in vivo. Adults m3. MALE Pets methods 5 weeks 6 weeks C57BL/6N Mice weighing 19 21 g were obtained from Charles River Laboratories AT7867 The animals were housed under ambient temperature and 12/12 hour light / dark cycle with free access to food and water. All experiments were performed in accordance with the National Institutes of Health guidelines for the use of laboratory animals. Both the Committee on Animal Care and the University t of Bundesbeh Gestures for animal experiments Gie S Regierungspr BUREAU approved the study protocol. Bleomycin administration and treatment groups on day 0, the Mice again U An Anesthesia Orotracheal instillation with isoflurane by supplying Llige bleomycin or saline Solution followed by sterile mouse nose pinched held.
Bleomycin in sterile saline Solution gel St was administered at a dose of 2.8 units / kg. The animals were assigned to the following groups: 1 “saline solution”, 2 “bleoctrl” and re 3 “Saline” group “Bleocilo.” U instillation of sterile saline solution On day 0 and re U vehicles. Mouse “bleoctrl” group re U of bleomycin instillation on day 0 and re U vehicles. Mouse re “bleocilo” group U of bleomycin instillation on day 0 and were once t Resembled treated with 50 mg / kg] Cyclohexancarbons Ure cilomilast Inc., suspended in the vehicle. L were solutions Orally feeding needle all be administered in the same way. Started treatment in all groups at day 0 and continued until the end of the experiment, that is t For 4, 7, 14 or 24 days.
Bronchoalveol Re lavage cell count of days 4 and 7 after the bleomycin instillation, the M Get use by injection of a lethal dose of pentobarbital Tet. The lungs were rinsed three times with 0.5 ml ice-cold PBSEDTA centrifuged was recovered liquid and the cell pellet was resuspended in 1 ml of saline ice. Total number of cells has been select using Neubauer Z. Derived cells Zellz COOLING were in a constant volume of 0.2 ml PBS transferred to a glass plate with 3 cytospin centrifuge and stained May Green Forest / Giemsa. The number of macrophages, neutrophils and lymphocytes were select by Z Determined optical microscope 100 from the total number of cells. This data was then extrapolated to the number of cells per milliliter. Lung compliance and histology on days 14 and 24 after the bleomycin instillation Mice were used to measure the compliance of the lung, subject as described above.