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Title
Japanese: 
English:Targeted disruption of Ig-Hepta/Gpr116 causes emphysema-like symptoms that are associated with alveolar macrophage activation 
Author
Japanese: アリエスタンティドンナマレッタ, 安東輝, 広瀬茂久, 中村信大.  
English: Donna Maretta Ariestanti, Hikaru Ando, SHIGEHISA HIROSE, Nobuhiro Nakamura.  
Language English 
Journal/Book name
Japanese:Journal of Biological Chemistry 
English: 
Volume, Number, Page Vol. 290    No. 17    pp. 11032-11040
Published date Apr. 24, 2015 
Publisher
Japanese: 
English:The American Society for Biochemistry and Molecular Biology 
Conference name
Japanese: 
English: 
Conference site
Japanese: 
English: 
DOI https://doi.org/10.1074/jbc.M115.648311
Abstract Ig-Hepta/GPR116 is a member of the G protein-coupled receptor family predominantly expressed in the alveolar type II epithelial cells of the lung. Previous studies have shown that Ig-Hepta is essential for lung surfactant homeostasis, and loss of its function results in high accumulation of surfactant lipids and proteins in the alveolar space. Ig-Hepta knock-out (Ig-Hepta(-/-)) mice also exhibit emphysema-like symptoms, including accumulation of foamy alveolar macrophages (AMs), but its pathogenic mechanism is unknown. Here, we show that the bronchoalveolar lavage fluid obtained from Ig-Hepta(-/-) mice contains high levels of inflammatory mediators, lipid hydroperoxides, and matrix metalloproteinases (MMPs), which are produced by AMs. Accumulation of reactive oxygen species was observed in the AMs of Ig-Hepta(-/-) mice in an age-dependent manner. In addition, nuclear factor-κB (NF-κB) is activated and translocated into the nuclei of the AMs of Ig-Hepta(-/-) mice. Release of MMP-2 and MMP-9 from the AMs was strongly inhibited by treatment with inhibitors of oxidants and NF-κB. We also found that the level of monocyte chemotactic protein-1 is increased in the embryonic lungs of Ig-Hepta(-/-) mice at 18.5 days postcoitum, when AMs are not accumulated and activated. These results suggest that Ig-Hepta plays an important role in regulating macrophage immune responses, and its deficiency leads to local inflammation in the lung, where AMs produce excessive amounts of reactive oxygen species and up-regulate MMPs through the NF-κB signaling pathway.

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