Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1782520792066555904 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5386570 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT liuhaijun bbc3inmacrophagespromotedpulmonaryfibrosisdevelopmentthroughinducingautophagyduringsilicosis AT chengyusi bbc3inmacrophagespromotedpulmonaryfibrosisdevelopmentthroughinducingautophagyduringsilicosis AT yangjian bbc3inmacrophagespromotedpulmonaryfibrosisdevelopmentthroughinducingautophagyduringsilicosis AT wangwei bbc3inmacrophagespromotedpulmonaryfibrosisdevelopmentthroughinducingautophagyduringsilicosis AT fangshencun bbc3inmacrophagespromotedpulmonaryfibrosisdevelopmentthroughinducingautophagyduringsilicosis AT zhangwei bbc3inmacrophagespromotedpulmonaryfibrosisdevelopmentthroughinducingautophagyduringsilicosis AT hanbing bbc3inmacrophagespromotedpulmonaryfibrosisdevelopmentthroughinducingautophagyduringsilicosis AT zhouzewei bbc3inmacrophagespromotedpulmonaryfibrosisdevelopmentthroughinducingautophagyduringsilicosis AT yaohonghong bbc3inmacrophagespromotedpulmonaryfibrosisdevelopmentthroughinducingautophagyduringsilicosis AT chaojie bbc3inmacrophagespromotedpulmonaryfibrosisdevelopmentthroughinducingautophagyduringsilicosis AT liaohong bbc3inmacrophagespromotedpulmonaryfibrosisdevelopmentthroughinducingautophagyduringsilicosis |