SPIONs enhances IL-10-producing macrophages to relieve sepsis via Cav1-Notch1/HES1-mediated autophagy

Yujun Xu,1 Yi Li,1 Xinghan Liu,1 Yuchen Pan,1 Zhiheng Sun,1 Yaxian Xue,1 Tingting Wang,1,2 Huan Dou,1,2 Yayi Hou1,21The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, People’s Republic of China; 2Jiangsu Key...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xu Y, Li Y, Liu X, Pan Y, Sun Z, Xue Y, Wang T, Dou H, Hou Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	SPIONs autophagy IL-10 liver injury sepsis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/35b8b11a47a340e8bb3a289e3cbceaaf
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:35b8b11a47a340e8bb3a289e3cbceaaf
record_format	dspace
spelling	oai:doaj.org-article:35b8b11a47a340e8bb3a289e3cbceaaf2021-12-02T09:26:14ZSPIONs enhances IL-10-producing macrophages to relieve sepsis via Cav1-Notch1/HES1-mediated autophagy1178-2013https://doaj.org/article/35b8b11a47a340e8bb3a289e3cbceaaf2019-08-01T00:00:00Zhttps://www.dovepress.com/spions-enhances-il-10-producing-macrophages-to-relieve-sepsis-via-cav1-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yujun Xu,1 Yi Li,1 Xinghan Liu,1 Yuchen Pan,1 Zhiheng Sun,1 Yaxian Xue,1 Tingting Wang,1,2 Huan Dou,1,2 Yayi Hou1,21The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, People’s Republic of China; 2Jiangsu Key Laboratory of Molecular Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, People’s Republic of ChinaCorrespondence: Huan Dou, Yayi HouThe State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, 22 Hankou Road, Nanjing 210093, People’s Republic of ChinaTel +86 25 8368 6043Fax +86 25 8368 6043Email douhuan@nju.edu.cn yayihou@nju.edu.cnBackground: Sepsis is a life-threatening condition caused by dysregulated host responses to infection. Macrophages, which recognize microbial infections through identification of bacterial markers such as lipopolysaccharide (LPS), are crucial to the pathogenesis of sepsis-associated liver injury. However, the understanding of the SPIONs-mediated modulation of macrophage responses in LPS-induced sepsis and liver injury is limited.Materials and methods: Superparamagnetic iron oxide nanoparticles (SPIONs) of γ-Fe2O3 nanoparticles were prepared, and their morphology and magnetic properties were characterized.Results: Using a murine model of LPS-induced sepsis and liver injury, we found that SPIONs alleviated LPS-induced sepsis, preventing infiltration of inflammatory cells into the liver. SPIONs also increased the level of interleukin-10 (IL-10) in liver macrophages, while SPIONs’s effect on LPS-induced sepsis was abrogated in IL-10-/-, mice, indicating that the protective effect of SPIONs is dependent on IL-10+, macrophages. Moreover, SPIONs activated macrophage autophagy to increase IL-10 production, which was markedly attenuated by autophagy inhibition. Furthermore, SPIONs upregulated the expression of Caveolin-1 (Cav1) in macrophages, which plays a role in cellular uptake of metallic nanoparticles. Interestingly, activation of Cav1 and Notch1/HES1 signaling was involved in SPIONs-induced autophagy in both RAW 264.7 cells and bone marrow-derived macrophages (BMDMs). Our data reveal a novel mechanism for SPIONs -induced autophagy in macrophages, which occurs through activation of the Cav1-Notch1/HES1 signaling pathway, which promotes the production of IL-10 in macrophages, leading to inhibition of inflammation in LPS-induced sepsis and liver injury.Conclusion: Our results suggest that SPIONs may represent a potential therapeutic agent for the treatment of sepsis and sepsis-induced liver injury.Keywords: SPIONs, autophagy, IL-10, liver injury, sepsis  Xu YLi YLiu XPan YSun ZXue YWang TDou HHou YDove Medical PressarticleSPIONsautophagyIL-10liver injurysepsisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 6779-6797 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	SPIONs autophagy IL-10 liver injury sepsis Medicine (General) R5-920
spellingShingle	SPIONs autophagy IL-10 liver injury sepsis Medicine (General) R5-920 Xu Y Li Y Liu X Pan Y Sun Z Xue Y Wang T Dou H Hou Y SPIONs enhances IL-10-producing macrophages to relieve sepsis via Cav1-Notch1/HES1-mediated autophagy
description	Yujun Xu,1 Yi Li,1 Xinghan Liu,1 Yuchen Pan,1 Zhiheng Sun,1 Yaxian Xue,1 Tingting Wang,1,2 Huan Dou,1,2 Yayi Hou1,21The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, People’s Republic of China; 2Jiangsu Key Laboratory of Molecular Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, People’s Republic of ChinaCorrespondence: Huan Dou, Yayi HouThe State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, 22 Hankou Road, Nanjing 210093, People’s Republic of ChinaTel +86 25 8368 6043Fax +86 25 8368 6043Email douhuan@nju.edu.cn yayihou@nju.edu.cnBackground: Sepsis is a life-threatening condition caused by dysregulated host responses to infection. Macrophages, which recognize microbial infections through identification of bacterial markers such as lipopolysaccharide (LPS), are crucial to the pathogenesis of sepsis-associated liver injury. However, the understanding of the SPIONs-mediated modulation of macrophage responses in LPS-induced sepsis and liver injury is limited.Materials and methods: Superparamagnetic iron oxide nanoparticles (SPIONs) of γ-Fe2O3 nanoparticles were prepared, and their morphology and magnetic properties were characterized.Results: Using a murine model of LPS-induced sepsis and liver injury, we found that SPIONs alleviated LPS-induced sepsis, preventing infiltration of inflammatory cells into the liver. SPIONs also increased the level of interleukin-10 (IL-10) in liver macrophages, while SPIONs’s effect on LPS-induced sepsis was abrogated in IL-10-/-, mice, indicating that the protective effect of SPIONs is dependent on IL-10+, macrophages. Moreover, SPIONs activated macrophage autophagy to increase IL-10 production, which was markedly attenuated by autophagy inhibition. Furthermore, SPIONs upregulated the expression of Caveolin-1 (Cav1) in macrophages, which plays a role in cellular uptake of metallic nanoparticles. Interestingly, activation of Cav1 and Notch1/HES1 signaling was involved in SPIONs-induced autophagy in both RAW 264.7 cells and bone marrow-derived macrophages (BMDMs). Our data reveal a novel mechanism for SPIONs -induced autophagy in macrophages, which occurs through activation of the Cav1-Notch1/HES1 signaling pathway, which promotes the production of IL-10 in macrophages, leading to inhibition of inflammation in LPS-induced sepsis and liver injury.Conclusion: Our results suggest that SPIONs may represent a potential therapeutic agent for the treatment of sepsis and sepsis-induced liver injury.Keywords: SPIONs, autophagy, IL-10, liver injury, sepsis
format	article
author	Xu Y Li Y Liu X Pan Y Sun Z Xue Y Wang T Dou H Hou Y
author_facet	Xu Y Li Y Liu X Pan Y Sun Z Xue Y Wang T Dou H Hou Y
author_sort	Xu Y
title	SPIONs enhances IL-10-producing macrophages to relieve sepsis via Cav1-Notch1/HES1-mediated autophagy
title_short	SPIONs enhances IL-10-producing macrophages to relieve sepsis via Cav1-Notch1/HES1-mediated autophagy
title_full	SPIONs enhances IL-10-producing macrophages to relieve sepsis via Cav1-Notch1/HES1-mediated autophagy
title_fullStr	SPIONs enhances IL-10-producing macrophages to relieve sepsis via Cav1-Notch1/HES1-mediated autophagy
title_full_unstemmed	SPIONs enhances IL-10-producing macrophages to relieve sepsis via Cav1-Notch1/HES1-mediated autophagy
title_sort	spions enhances il-10-producing macrophages to relieve sepsis via cav1-notch1/hes1-mediated autophagy
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/35b8b11a47a340e8bb3a289e3cbceaaf
work_keys_str_mv	AT xuy spionsenhancesil10producingmacrophagestorelievesepsisviacav1notch1hes1mediatedautophagy AT liy spionsenhancesil10producingmacrophagestorelievesepsisviacav1notch1hes1mediatedautophagy AT liux spionsenhancesil10producingmacrophagestorelievesepsisviacav1notch1hes1mediatedautophagy AT pany spionsenhancesil10producingmacrophagestorelievesepsisviacav1notch1hes1mediatedautophagy AT sunz spionsenhancesil10producingmacrophagestorelievesepsisviacav1notch1hes1mediatedautophagy AT xuey spionsenhancesil10producingmacrophagestorelievesepsisviacav1notch1hes1mediatedautophagy AT wangt spionsenhancesil10producingmacrophagestorelievesepsisviacav1notch1hes1mediatedautophagy AT douh spionsenhancesil10producingmacrophagestorelievesepsisviacav1notch1hes1mediatedautophagy AT houy spionsenhancesil10producingmacrophagestorelievesepsisviacav1notch1hes1mediatedautophagy
_version_	1718398113527365632

SPIONs enhances IL-10-producing macrophages to relieve sepsis via Cav1-Notch1/HES1-mediated autophagy

Ejemplares similares