Macrophage-derived MCPIP1 mediates silica-induced pulmonary fibrosis via autophagyReportar como inadecuado

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Particle and Fibre Toxicology

, 13:55

First Online: 25 October 2016Received: 01 July 2016Accepted: 13 October 2016DOI: 10.1186-s12989-016-0167-z

Cite this article as: Liu, H., Fang, S., Wang, W. et al. Part Fibre Toxicol 2016 13: 55. doi:10.1186-s12989-016-0167-z


BackgroundSilicosis is characterized by accumulation of fibroblasts and excessive deposition of extracellular matrix. Monocyte chemotactic protein-1-induced protein 1 MCPIP1 plays a critical role in fibrosis induced by SiO2. However, the details of the downstream events of MCPIP1 activity in pulmonary fibrosis remain unclear. To elucidate the role of MCPIP1-induced autophagy in SiO2-induced fibrosis, both the upstream molecular mechanisms and the functional effects of SiO2 on cell apoptosis, proliferation and migration were investigated.

ResultsExperiments using primary cultures of alveolar macrophages from healthy donors and silicosis patients as well as differentiated U937 macrophages demonstrated the following results: 1 SiO2 induced macrophage autophagy in association with enhanced expression of MCPIP1; 2 autophagy promoted apoptosis and activation of macrophages exposed to SiO2, and these events induced the development of silicosis; 3 MCPIP1 facilitated macrophage apoptosis and activation via p53 signaling-mediated autophagy; and 4 SiO2-activated macrophages promoted the proliferation and migration of fibroblasts via the MCPIP1-p53-mediated autophagy pathway.

ConclusionsOur results elucidated a link between SiO2-induced fibrosis and MCPIP1-p53 signaling-mediated autophagy. These findings provide novel insight into the potential targeting of MCPIP1 or autophagy in the development of potential therapeutic strategies for silicosis.

KeywordsAutophagy MCPIP1 Silicosis p53 Migration Abbreviations3-MA3-methyladenine

AMDGFAlveolar macrophage-derived growth factor

BALFBronchoalveolar lavage fluid

CCL2C-C chemokine ligand 2

CCR2C-C chemokine receptor 2

COPDChronic obstructive pulmonary disease

DMEMDulbecco-s modified eagle-s medium

FBSFetal bovine serum

HPF-aHuman pulmonary fibroblasts-adult

iNOSInducible nitric oxide synthase

IPFIdiopathic pulmonary fibrosis

MCP-1Monocyte chemotactic protein-1

MCPIP1Monocyte chemotactic protein-1-induced protein 1

MTT3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide

NGSNormal goat serum

NSNormal saline

PAHPulmonary arterial hypertension

PMAPhorbol myristate acetate

SiO2Silicon dioxide

siRNASmall interference RNA

SOCS3Suppressor of cytokine signaling 3

α-SMAα smooth muscle actin

Electronic supplementary materialThe online version of this article doi:10.1186-s12989-016-0167-z contains supplementary material, which is available to authorized users.

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Autor: Haijun Liu - Shencun Fang - Wei Wang - Yusi Cheng - Yingming Zhang - Hong Liao - Honghong Yao - Jie Chao


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