Roles of macrophage exosomes in immune response to calcium oxalate monohydrate crystals
© 2018 Singhto, Kanlaya, Nilnumkhum and Thongboonkerd. In kidney stone disease, macrophages secrete various mediators via classical secretory pathway and cause renal interstitial inflammation. However, whether their extracellular vesicles, particularly exosomes, are involved in kidney stone pathogen...
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th-mahidol.460452019-08-28T13:23:25Z Roles of macrophage exosomes in immune response to calcium oxalate monohydrate crystals Nilubon Singhto Rattiyaporn Kanlaya Angkhana Nilnumkhum Visith Thongboonkerd Mahidol University Faculty of Medicine, Siriraj Hospital, Mahidol University Immunology and Microbiology Medicine © 2018 Singhto, Kanlaya, Nilnumkhum and Thongboonkerd. In kidney stone disease, macrophages secrete various mediators via classical secretory pathway and cause renal interstitial inflammation. However, whether their extracellular vesicles, particularly exosomes, are involved in kidney stone pathogenesis remained unknown. This study investigated alterations in exosomal proteome of U937-derived macrophages (by phorbol-12-myristate-13-acetate activation) after exposure to calcium oxalate monohydrate (COM) crystals for 16-h using 2-DE-based proteomics approach. Six significantly altered proteins in COM-treated exosomes were successfully identified by nanoscale liquid chromatography-electrospray ionization-electron transfer dissociation tandem mass spectrometry as proteins involved mainly in immune processes, including T-cell activation and homeostasis, Fcγ receptor-mediated phagocytosis, interferon-γ (IFN-γ) regulation, and cell migration/movement. The decreased heat shock protein 90-beta (HSP90β) and increased vimentin were confirmed by Western blotting. ELISA showed that the COM-treated macrophages produced greater level of interleukin-1β (IL-1β), one of the markers for inflammasome activation. Functional studies demonstrated that COM-treated exosomes enhanced monocyte and T-cell migration, monocyte activation and macrophage phagocytic activity, but on the other hand, reduced T-cell activation. In addition, COM-treated exosomes enhanced production of proinflammatory cytokine IL-8 by monocytes that could be restored to its basal level by small-interfering RNA targeting on vimentin (si-Vimentin). Moreover, si-Vimentin could also abolish effects of COM-treated exosomes on monocyte and T-cell migration as well as macrophage phagocytic activity. These findings provided some implications to the immune response during kidney stone pathogenesis via exosomal pathway of macrophages after exposure to COM crystals. 2019-08-23T11:22:36Z 2019-08-23T11:22:36Z 2018-02-27 Article Frontiers in Immunology. Vol.9, No.FEB (2018) 10.3389/fimmu.2018.00316 16643224 2-s2.0-85042713665 https://repository.li.mahidol.ac.th/handle/123456789/46045 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85042713665&origin=inward |
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Immunology and Microbiology Medicine Nilubon Singhto Rattiyaporn Kanlaya Angkhana Nilnumkhum Visith Thongboonkerd Roles of macrophage exosomes in immune response to calcium oxalate monohydrate crystals |
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© 2018 Singhto, Kanlaya, Nilnumkhum and Thongboonkerd. In kidney stone disease, macrophages secrete various mediators via classical secretory pathway and cause renal interstitial inflammation. However, whether their extracellular vesicles, particularly exosomes, are involved in kidney stone pathogenesis remained unknown. This study investigated alterations in exosomal proteome of U937-derived macrophages (by phorbol-12-myristate-13-acetate activation) after exposure to calcium oxalate monohydrate (COM) crystals for 16-h using 2-DE-based proteomics approach. Six significantly altered proteins in COM-treated exosomes were successfully identified by nanoscale liquid chromatography-electrospray ionization-electron transfer dissociation tandem mass spectrometry as proteins involved mainly in immune processes, including T-cell activation and homeostasis, Fcγ receptor-mediated phagocytosis, interferon-γ (IFN-γ) regulation, and cell migration/movement. The decreased heat shock protein 90-beta (HSP90β) and increased vimentin were confirmed by Western blotting. ELISA showed that the COM-treated macrophages produced greater level of interleukin-1β (IL-1β), one of the markers for inflammasome activation. Functional studies demonstrated that COM-treated exosomes enhanced monocyte and T-cell migration, monocyte activation and macrophage phagocytic activity, but on the other hand, reduced T-cell activation. In addition, COM-treated exosomes enhanced production of proinflammatory cytokine IL-8 by monocytes that could be restored to its basal level by small-interfering RNA targeting on vimentin (si-Vimentin). Moreover, si-Vimentin could also abolish effects of COM-treated exosomes on monocyte and T-cell migration as well as macrophage phagocytic activity. These findings provided some implications to the immune response during kidney stone pathogenesis via exosomal pathway of macrophages after exposure to COM crystals. |
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Mahidol University |
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Mahidol University Nilubon Singhto Rattiyaporn Kanlaya Angkhana Nilnumkhum Visith Thongboonkerd |
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Article |
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Nilubon Singhto Rattiyaporn Kanlaya Angkhana Nilnumkhum Visith Thongboonkerd |
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Nilubon Singhto |
title |
Roles of macrophage exosomes in immune response to calcium oxalate monohydrate crystals |
title_short |
Roles of macrophage exosomes in immune response to calcium oxalate monohydrate crystals |
title_full |
Roles of macrophage exosomes in immune response to calcium oxalate monohydrate crystals |
title_fullStr |
Roles of macrophage exosomes in immune response to calcium oxalate monohydrate crystals |
title_full_unstemmed |
Roles of macrophage exosomes in immune response to calcium oxalate monohydrate crystals |
title_sort |
roles of macrophage exosomes in immune response to calcium oxalate monohydrate crystals |
publishDate |
2019 |
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https://repository.li.mahidol.ac.th/handle/123456789/46045 |
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1763489356680527872 |