Hailin Zhang1, Sha Chen2, Meichun Zeng3, Daopeng Lin1, Yu Wang2, Xunhang Wen1, Changfu Xu1, Li Yang4, Xiaofang Fan2, Yongsheng Gong2, Hongyu Zhang5, Xiaoxia Kong2. 1. Department of Children's Respiration, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China. 2. School of Basic Medical Sciences, Institute of Hypoxia Research, Wenzhou Medical University, Wenzhou, China. 3. Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. 4. Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 5. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
Abstract
BACKGROUND/AIMS: Acute lung injury (ALI) is induced by a variety of external and internal factors and leads to acute progressive respiratory failure. Previous studies have shown that apelin-13 can decrease the acute lung injury induced by LPS, but the specific mechanism is unclear. Therefore, a mouse lung injury model and a cell model were designed to explore the mechanism of how apelin-13 alleviates the acute lung injury caused by LPS. METHODS: The effect of apelin-13 on LPS-induced structural damage was determined by H&E staining and by the wet/dry weight ratio. The related inflammatory factors in BALF were examined by ELISA. The apoptotic pathway and the NF-κB and NLRP3 inflammasome pathways were evaluated by using Western blotting and immunofluorescence staining. RESULTS: LPS induced the structural damage and the production of inflammatory cytokines in the lung tissues of mice. These deleterious effects were attenuated by apelin-13 administration. The protective effects of apelin-13 were associated with decreased reactive oxygen species (ROS) formation and the inhibition of the activation of the NF-κB and NLRP3 inflammasome pathways in mice and in Raw264.7 cells. CONCLUSION: Taken together, these data suggest that apelin-13 administration ameliorates LPS-induced acute lung injury by suppressing ROS formation, as well as by inhibiting the NF-κB pathway and the activation of the NLRP3 inflammasome in the lungs.
BACKGROUND/AIMS: Acute lung injury (ALI) is induced by a variety of external and internal factors and leads to acute progressive respiratory failure. Previous studies have shown that apelin-13 can decrease the acute lung injury induced by LPS, but the specific mechanism is unclear. Therefore, a mouselung injury model and a cell model were designed to explore the mechanism of how apelin-13 alleviates the acute lung injury caused by LPS. METHODS: The effect of apelin-13 on LPS-induced structural damage was determined by H&E staining and by the wet/dry weight ratio. The related inflammatory factors in BALF were examined by ELISA. The apoptotic pathway and the NF-κB and NLRP3 inflammasome pathways were evaluated by using Western blotting and immunofluorescence staining. RESULTS:LPS induced the structural damage and the production of inflammatory cytokines in the lung tissues of mice. These deleterious effects were attenuated by apelin-13 administration. The protective effects of apelin-13 were associated with decreased reactive oxygen species (ROS) formation and the inhibition of the activation of the NF-κB and NLRP3 inflammasome pathways in mice and in Raw264.7 cells. CONCLUSION: Taken together, these data suggest that apelin-13 administration ameliorates LPS-induced acute lung injury by suppressing ROS formation, as well as by inhibiting the NF-κB pathway and the activation of the NLRP3 inflammasome in the lungs.
Authors: Duuamene Nyimanu; Richard G Kay; Petra Sulentic; Rhoda E Kuc; Philip Ambery; Lutz Jermutus; Frank Reimann; Fiona M Gribble; Joseph Cheriyan; Janet J Maguire; Anthony P Davenport Journal: Sci Rep Date: 2019-12-27 Impact factor: 4.379