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BBC3 in macrophages promoted pulmonary fibrosis development through inducing autophagy during silicosis

Following inhalation into the lungs, silica particles are engulfed by alveolar macrophages, which triggers endogenous or exogenous apoptosis signaling pathways. As an inducer of apoptosis, the role of BBC3/PUMA (BCL2-binding component 3) in macrophages during silicosis remains unknown. Here, we expo...

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Autores principales: Liu, Haijun, Cheng, Yusi, Yang, Jian, Wang, Wei, Fang, Shencun, Zhang, Wei, Han, Bing, Zhou, Zewei, Yao, Honghong, Chao, Jie, Liao, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386570/
https://www.ncbi.nlm.nih.gov/pubmed/28277537
http://dx.doi.org/10.1038/cddis.2017.78
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author Liu, Haijun
Cheng, Yusi
Yang, Jian
Wang, Wei
Fang, Shencun
Zhang, Wei
Han, Bing
Zhou, Zewei
Yao, Honghong
Chao, Jie
Liao, Hong
author_facet Liu, Haijun
Cheng, Yusi
Yang, Jian
Wang, Wei
Fang, Shencun
Zhang, Wei
Han, Bing
Zhou, Zewei
Yao, Honghong
Chao, Jie
Liao, Hong
author_sort Liu, Haijun
collection PubMed
description Following inhalation into the lungs, silica particles are engulfed by alveolar macrophages, which triggers endogenous or exogenous apoptosis signaling pathways. As an inducer of apoptosis, the role of BBC3/PUMA (BCL2-binding component 3) in macrophages during silicosis remains unknown. Here, we exposed U937 cell-derived macrophages (UDMs) to SiO(2) in vitro to explore the function of BBC3 in SiO(2)-induced disease. We found that SiO(2) induced increased BBC3 expression, as well as macrophage activation and apoptosis. Knockdown of Bbc3 with specific siRNA significantly mitigated the SiO(2)-induced effects. In addition, our results clearly showed increased levels of autophagy in macrophages exposed to SiO(2). However, inhibition of BBC3 decreased the occurrence of autophagy. Furthermore, we observed that the blockade of autophagy with 3-MA, an autophagy inhibitor, inhibited SiO(2)-induced macrophage activation and apoptosis. In contrast, rapamycin, an autophagy inducer, further enhanced the effects induced by SiO(2). The conditioned medium from macrophages exposed to SiO(2) promoted the proliferation and migration of fibroblasts, and the inhibition of BBC3/autophagy reduced the effects of the conditioned medium on fibroblasts. In the mouse model of silicosis, Bbc3 knockout mice clearly exhibited decreased levels of autophagy and fibrosis progression. These results suggest that downregulation of BBC3 expression may become a novel therapeutic strategy for the treatment of silicosis.
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spelling pubmed-53865702017-04-27 BBC3 in macrophages promoted pulmonary fibrosis development through inducing autophagy during silicosis Liu, Haijun Cheng, Yusi Yang, Jian Wang, Wei Fang, Shencun Zhang, Wei Han, Bing Zhou, Zewei Yao, Honghong Chao, Jie Liao, Hong Cell Death Dis Original Article Following inhalation into the lungs, silica particles are engulfed by alveolar macrophages, which triggers endogenous or exogenous apoptosis signaling pathways. As an inducer of apoptosis, the role of BBC3/PUMA (BCL2-binding component 3) in macrophages during silicosis remains unknown. Here, we exposed U937 cell-derived macrophages (UDMs) to SiO(2) in vitro to explore the function of BBC3 in SiO(2)-induced disease. We found that SiO(2) induced increased BBC3 expression, as well as macrophage activation and apoptosis. Knockdown of Bbc3 with specific siRNA significantly mitigated the SiO(2)-induced effects. In addition, our results clearly showed increased levels of autophagy in macrophages exposed to SiO(2). However, inhibition of BBC3 decreased the occurrence of autophagy. Furthermore, we observed that the blockade of autophagy with 3-MA, an autophagy inhibitor, inhibited SiO(2)-induced macrophage activation and apoptosis. In contrast, rapamycin, an autophagy inducer, further enhanced the effects induced by SiO(2). The conditioned medium from macrophages exposed to SiO(2) promoted the proliferation and migration of fibroblasts, and the inhibition of BBC3/autophagy reduced the effects of the conditioned medium on fibroblasts. In the mouse model of silicosis, Bbc3 knockout mice clearly exhibited decreased levels of autophagy and fibrosis progression. These results suggest that downregulation of BBC3 expression may become a novel therapeutic strategy for the treatment of silicosis. Nature Publishing Group 2017-03 2017-03-09 /pmc/articles/PMC5386570/ /pubmed/28277537 http://dx.doi.org/10.1038/cddis.2017.78 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Liu, Haijun
Cheng, Yusi
Yang, Jian
Wang, Wei
Fang, Shencun
Zhang, Wei
Han, Bing
Zhou, Zewei
Yao, Honghong
Chao, Jie
Liao, Hong
BBC3 in macrophages promoted pulmonary fibrosis development through inducing autophagy during silicosis
title BBC3 in macrophages promoted pulmonary fibrosis development through inducing autophagy during silicosis
title_full BBC3 in macrophages promoted pulmonary fibrosis development through inducing autophagy during silicosis
title_fullStr BBC3 in macrophages promoted pulmonary fibrosis development through inducing autophagy during silicosis
title_full_unstemmed BBC3 in macrophages promoted pulmonary fibrosis development through inducing autophagy during silicosis
title_short BBC3 in macrophages promoted pulmonary fibrosis development through inducing autophagy during silicosis
title_sort bbc3 in macrophages promoted pulmonary fibrosis development through inducing autophagy during silicosis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386570/
https://www.ncbi.nlm.nih.gov/pubmed/28277537
http://dx.doi.org/10.1038/cddis.2017.78
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