Jiakun Tian1, Xiaoqian Cui1, Jian Sun1, Jingxiao Zhang2. 1. Department of Critical Care Medicine, The Second Hospital of Jilin University, Changchun 130021, Jilin Provence, China. 2. Department of Critical Care Medicine, The Second Hospital of Jilin University, Changchun 130021, Jilin Provence, China. Electronic address: zhangjingxiao@jlu.edu.cn.
Abstract
OBJECTIVE: Reports on septic lung injury have implicated the protective effects of adipose mesenchymal stem cells-derived Exos (ADSCs-Exos). At present, we tried to explain the mechanism of ADSCs-Exos-loaded microRNA (miR)-16-5p in inflammatory response and macrophage polarization by regulating Toll-like Receptor 4 (TLR4). METHODS: ADSCs-Exos were obtained and transfected with miR-16-5p agomir. The septic lung injury model was induced by cecal ligation and puncture and the modeled mice were injected with the Exos or silenced TLR4 vector, after which inflammation, pathological changes, macrophage polarization in the lung tissue were monitored. In vitro RAW246.7 macrophages were stimulated by lipopolysaccharide (LPS), interfered with Exos or TLR4-related vector and detected for inflammatory response. RESULTS: ADSCs-Exos reduced lung injury in septic mice and promoted M2 polarization. Up-regulating exosomal miR-16-5p inhibited macrophage inflammation and relieved lung injury in septic mice. Silencing TLR4 improved lung inflammation while overexpression of TLR4 impaired the impact of exosomal miR-16-5p in septic mice. Restoration of TLR4 reduced the impact of exosomal miR-16-5p on LPS-treated RAW 264.7 macrophages. CONCLUSION: Exosomal miR-16-5p from ADSCs promotes macrophage polarization and attenuates septic lung injury in mice via suppressing TLR4.
OBJECTIVE: Reports on septic lung injury have implicated the protective effects of adipose mesenchymal stem cells-derived Exos (ADSCs-Exos). At present, we tried to explain the mechanism of ADSCs-Exos-loaded microRNA (miR)-16-5p in inflammatory response and macrophage polarization by regulating Toll-like Receptor 4 (TLR4). METHODS: ADSCs-Exos were obtained and transfected with miR-16-5p agomir. The septic lung injury model was induced by cecal ligation and puncture and the modeled mice were injected with the Exos or silenced TLR4 vector, after which inflammation, pathological changes, macrophage polarization in the lung tissue were monitored. In vitro RAW246.7 macrophages were stimulated by lipopolysaccharide (LPS), interfered with Exos or TLR4-related vector and detected for inflammatory response. RESULTS: ADSCs-Exos reduced lung injury in septic mice and promoted M2 polarization. Up-regulating exosomal miR-16-5p inhibited macrophage inflammation and relieved lung injury in septic mice. Silencing TLR4 improved lung inflammation while overexpression of TLR4 impaired the impact of exosomal miR-16-5p in septic mice. Restoration of TLR4 reduced the impact of exosomal miR-16-5p on LPS-treated RAW 264.7 macrophages. CONCLUSION: Exosomal miR-16-5p from ADSCs promotes macrophage polarization and attenuates septic lung injury in mice via suppressing TLR4.
Authors: Desheng Tang; Feng Cao; Changsheng Yan; Kun Fang; Jiamin Ma; Lei Gao; Bei Sun; Gang Wang Journal: Front Immunol Date: 2022-06-13 Impact factor: 8.786