Oncotarget

Research Papers: Pathology:

Pulmonary fibrosis in a mouse model of sarcoid granulomatosis induced by booster challenge with Propionibacterium acnes

Dingyuan Jiang, Xiaoxi Huang, Jing Geng, Run Dong, Shuhong Li, Zheng Liu, Chen Wang and Huaping Dai _

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Oncotarget. 2016; 7:33703-33714. https://doi.org/10.18632/oncotarget.9397

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Abstract

Dingyuan Jiang1, Xiaoxi Huang2, Jing Geng1, Run Dong1, Shuhong Li1, Zheng Liu2, Chen Wang3 and Huaping Dai1,3

1 Department of Respiratory and Critical Care Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing Chao-Yang Hospital-Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, P.R. China

2 Department of Medical Research, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, P.R. China

3 Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, P.R. China

Correspondence to:

Huaping Dai, email:

Keywords: sarcoidosis, granuloma, inflammation, pulmonary fibrosis, mice, Pathology Section

Received: March 15, 2016 Accepted: April 27, 2016 Published: May 17, 2016

Abstract

Pulmonary fibrosis (PF) associated with chronic sarcoidosis remains poorly understood, and no experimental model is currently available for this condition. Previous studies have shown that Propionibacterium acnes (PA) was associated with sarcoidosis and induced granuloma formation in mice. Here, we investigated whether repeated challenge with PA induces persistent inflammation leading to sarcoidosis followed by PF in mice. Specifically, C57BL/6 mice were inoculated intraperitoneally and subjected to intratracheal challenge with PA, and then were booster-challenged with either PA or phosphate-buffered saline on day 28. Inflammation, granulomata, and features of fibrosis were evaluated every 7 days until day 70. Complete remission of lung granulomata was apparent on day 42 in the sarcoid-remission group. However, granulomata was present from days 21 to 70 in mice that received PA boosting. Inflammatory cell counts and Th1 cytokine levels in lung lavage fluids were elevated up to day 70. Furthermore, fibrotic changes in the lungs were observed around granulomatous and peribronchovascular regions after PA boosting. Taken together, these findings suggest that development of PF following sarcoidosis may result from continuous PA infection and inflammation. Repeated boosting with PA to induce PF might be a useful model for future studies of sarcoidosis-associated PF.


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