Abstract
Introduction: Chronic sarcoidosis associated pulmonary fibrosis(PF) has a negative impact on mortality, which was poorly understood and lack of experimental model. Previous studies showed self-remission granuloma in Propionibacterium acnes(PA)-boost mice. Gene expression researches suggested that fibrosis developed from sarcoidosis in the setting of inflammation.
Objectives: We investigated whether consistent inflammation induced by repeat boost with PA will lead to PF following sarcoidosis in mice.
Methods: C57BL/6 mice were inoculated intraperitoneally and boost intratracheally on day 14 and day 28 with heat killed PA (PBS as negative control). Mice inoculated and boost on day 14 were investigated as granuloma phase control. Inflammation, granuloma and fibrosis features were evaluated every 7 days until day 42 after last boost.
Results: Lung granulomas appeared in once boost mice on day 21 and regressed by self-remission on day 35. However the granulomas existed from day 21 to day 70 with a slower weaken pace in mice receiving second PA boosting. Moreover lung fibrotic changes appeared in the periphery of granulomas and peribronchovascular regions, TGF-β1 and collagen I were significantly increased at day 35 in repeated PA-boost mice compare to the control.
Conclusions: These findings suggest that PF following sarcoidosis may result from continuous infection and inflammation. Repeated PA boost induced PF may be a useful model for sarcoidosis associated PF investigation.
- Copyright ©ERS 2015