Simvastatin treatment boosts benefits of apoptotic cell infusion in murine lung fibrosis

Ye Ji Lee, Meung Joo Kim, Young So Yoon, Youn Hee Choi, Hee Sun Kim, Jihee Lee Kang

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18 Scopus citations


A single early-phase infusion of apoptotic cells can inhibit bleomycin-induced lung inflammation and fibrosis; however, it is unknown whether these effects can be enhanced with additional infusions and/or statin treatment. Here, we investigated whether an increased frequency of apoptotic cell injection, with or without efferocytosis enhancer simvastatin, facilitates therapeutic efficacy. An additional injection of apoptotic cells during the intermediate phase (7 days post-bleomycin treatment) or simvastatin administration alone on days 7–13 post-treatment did not promote anti-fibrotic responses beyond those induced by a single early apoptotic cell infusion alone. Additional administration of apoptotic cells with simvastatin further enhanced the efferocytic ability of alveolar macrophages and PPARγ activity, and induced hepatocyte growth factor and interleukin-10 expression, in alveolar macrophages and lung tissue. Additional administration of apoptotic cells with simvastatin also reduced mRNA expression of bleomycin-induced epithelial-mesenchymal transition (EMT) markers in isolated alveolar type II epithelial cells, fibrotic markers in fibroblasts, and hydroxyproline in lung tissue. Enhanced anti-EMT and anti-fibrotic efficacy was confirmed by immunofluores-cence and trichrome staining of lung tissue. This suggests that additional administration of apoptotic cells with simvastatin during the intermediate phase of bleomycin-induced lung fibrosis may boost the anti-fibrotic properties of early apoptotic cell infusion.

Original languageEnglish
Article numbere2860
JournalCell Death and Disease
Issue number6
StatePublished - 2017

Bibliographical note

Funding Information:
Acknowledgements. This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Science, ICT & Future Planning (2010-0027945).

Publisher Copyright:
© The Author(s) 2017.


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