Macrophage-derived MCPIP1 mediates silica-induced pulmonary fibrosis via autophagy

BACKGROUND: Silicosis 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 SiO(2). However, the details of the downstream events of MCPIP1 activity in pulmonary fibrosis remain unclear. To elucidate the role of MCPIP1-induced autophagy in SiO(2)-induced fibrosis, both the upstream molecular mechanisms and the functional effects of SiO(2) on cell apoptosis, proliferation and migration were investigated. RESULTS: Experiments using primary cultures of alveolar macrophages from healthy donors and silicosis patients as well as differentiated U937 macrophages demonstrated the following results: 1) SiO(2) induced macrophage autophagy in association with enhanced expression of MCPIP1; 2) autophagy promoted apoptosis and activation of macrophages exposed to SiO(2), and these events induced the development of silicosis; 3) MCPIP1 facilitated macrophage apoptosis and activation via p53 signaling-mediated autophagy; and 4) SiO(2)-activated macrophages promoted the proliferation and migration of fibroblasts via the MCPIP1/p53-mediated autophagy pathway. CONCLUSIONS: Our results elucidated a link between SiO(2)-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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-016-0167-z) contains supplementary material, which is available to authorized users.