Diffuse Lung Disease: Diffuse Lung Disease: Sarcoidosis |

Repeated Challenge With Propionibacterium Acnes-Induced Chronic Sarcoidosis With Pulmonary Fibrosis in C57BL/6 Mice FREE TO VIEW

Dingyuan Jiang; Huaping Dai, MD; Xiaoxi Huang
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Beijing Chao-Yang Hospital, Beijing, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A221. doi:10.1016/j.chest.2016.02.228
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SESSION TITLE: Diffuse Lung Disease: Sarcoidosis

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: 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. We investigated whether consistent inflammation induced by repeat boost with PA will lead to PF following sarcoidosis in mice.

METHODS: Mice were randomly divided into two experimental groups. C57BL/6 mice inoculated intraperitoneally with PA and then challenged intratracheally both on day 14 and day 28 with PA were investigated as sarcoid-fibrosis group. Mice inoculated and challenged on day 14 with PA while gave PBS challenging on day 28 were sarcoid-remission group. PBS inoculation and challenging on day 0, day 14 and day 28 were taken as negative control group. Inflammation, granuloma and fibrosis features were evaluated every 7 days from day 21 to day 70.

RESULTS: Lung granulomas appeared in experimental group on day 21. Granulomatous inflmmation in sarcoid-remission group got totally remission since day 35. However after repeated PA challeng on day 28, the granulomas existed till day 70 with a slower weaken pace in sarcoid-fibrosis group. Moreover lung fibrotic changes appeared in the periphery of granulomas and peribronchovascular regions. TGF-β1 and IL-17A were significantly increased from day 35 in sarcoid-fibrosis mice compare to the negative controls.

CONCLUSIONS: These findings suggest that PF following sarcoidosis may result from continuous infection and inflammation. Repeated boost with PA induced PF may be a useful model for sarcoidosis associated PF investigation.

CLINICAL IMPLICATIONS: Our research gave an enlightenment into the relationship between persistent inflammation and lung fibrosis in sarcoidosis. This investigation tried to establish a chronic sarcoidosis mouse model with pulmonary fibrosis, and it may be a useful tool to detect the mechanisms of pulmonary fibrotic sarcoidosis and more helpful to researches on disease treatment.

DISCLOSURE: The following authors have nothing to disclose: Dingyuan Jiang, Huaping Dai, Xiaoxi Huang

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