Lipocalin-2 Alleviates LPS-Induced Inflammation Through Alteration of Macrophage Properties

Huahua Du,1 Li Liang,1 Jiahui Li,1 Qingqing Xiong,1 Xin Yu,2 Hong Yu3 1MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Science, Zhejiang University, Zhejiang, 310058, People’s Republic of China; 2Department of Anesthesia, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang Un...

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Autores principales:	Du H, Liang L, Li J, Xiong Q, Yu X, Yu H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	lcn2 systemic inflammation macrophages bmdms Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/84ea15c760bc432a80d18f4cdb9aa1bc
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spelling	oai:doaj.org-article:84ea15c760bc432a80d18f4cdb9aa1bc2021-12-02T18:56:49ZLipocalin-2 Alleviates LPS-Induced Inflammation Through Alteration of Macrophage Properties1178-7031https://doaj.org/article/84ea15c760bc432a80d18f4cdb9aa1bc2021-08-01T00:00:00Zhttps://www.dovepress.com/lipocalin-2-alleviates-lps-induced-inflammation-through-alteration-of--peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Huahua Du,1 Li Liang,1 Jiahui Li,1 Qingqing Xiong,1 Xin Yu,2 Hong Yu3 1MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Science, Zhejiang University, Zhejiang, 310058, People’s Republic of China; 2Department of Anesthesia, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Zhejiang, 310016, People’s Republic of China; 3Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Zhejiang, 310016, People’s Republic of ChinaCorrespondence: Hong YuDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Zhejiang, 310016, People’s Republic of ChinaTel +86-571-86044817Fax +86-571-86090063Email blueyu000@zju.edu.cnPurpose: Lipocalin-2 (Lcn2) is an acute-phase protein and elevated in several inflammatory diseases. This study aimed to determine whether Lcn2 alleviates inflammation and explore the underlying cellular mechanisms.Methods: C57BL/6 Lcn2-deficient (Lcn2−/-) male mice were intraperitoneally injected with lipopolysaccharide (LPS) to build systemic inflammation model. The inflammatory processes were investigated. The morphology of villi was measured by scanning electron microscopy (SEM). The levels of inflammatory factors were detected by ELISA and qPCR analysis. The production of Lcn2 was determined with immunofluorescence staining by confocal microscope. The molecular mechanism of Lcn2 in bone marrow-derived macrophages (BMDMs) was analyzed by mass spectrometry (MS)-based quantitative proteomic analysis.Results: Compared to wild-type (WT) mice injected with LPS, Lcn2−/- mice injected with LPS showed increased inflammatory damage in jejunum and ileum, and significantly elevated the levels of multiple pro-inflammatory cytokines. After determining that Lcn2 was mainly located in the cytoplasm of macrophages, we isolated BMDMs from Lcn2−/- mice to evaluate their function. During LPS challenge, transcripts of pro-inflammatory cytokines were all significantly increased in BMDMs from Lcn2−/- mice, while those of anti-inflammatory cytokines were significantly decreased when compared with the cytokines in BMDMs from WT mice. A label-free relative quantitation proteomics analysis showed that LPS-treated BMDMs from Lcn2−/- mice had elevated levels of pro-inflammatory pathways, but reduced phagocytosis and autophagy when compared with LPS-treated BMDMs from WT mice.Conclusion: These findings demonstrated that Lcn2 was a potent protective factor in response to systemic inflammation and might be an indispensable factor for macrophage functions.Keywords: Lcn2, systemic inflammation, macrophages, BMDMsDu HLiang LLi JXiong QYu XYu HDove Medical Pressarticlelcn2systemic inflammationmacrophagesbmdmsPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 4189-4203 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lcn2 systemic inflammation macrophages bmdms Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	lcn2 systemic inflammation macrophages bmdms Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Du H Liang L Li J Xiong Q Yu X Yu H Lipocalin-2 Alleviates LPS-Induced Inflammation Through Alteration of Macrophage Properties
description	Huahua Du,1 Li Liang,1 Jiahui Li,1 Qingqing Xiong,1 Xin Yu,2 Hong Yu3 1MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Science, Zhejiang University, Zhejiang, 310058, People’s Republic of China; 2Department of Anesthesia, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Zhejiang, 310016, People’s Republic of China; 3Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Zhejiang, 310016, People’s Republic of ChinaCorrespondence: Hong YuDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Zhejiang, 310016, People’s Republic of ChinaTel +86-571-86044817Fax +86-571-86090063Email blueyu000@zju.edu.cnPurpose: Lipocalin-2 (Lcn2) is an acute-phase protein and elevated in several inflammatory diseases. This study aimed to determine whether Lcn2 alleviates inflammation and explore the underlying cellular mechanisms.Methods: C57BL/6 Lcn2-deficient (Lcn2−/-) male mice were intraperitoneally injected with lipopolysaccharide (LPS) to build systemic inflammation model. The inflammatory processes were investigated. The morphology of villi was measured by scanning electron microscopy (SEM). The levels of inflammatory factors were detected by ELISA and qPCR analysis. The production of Lcn2 was determined with immunofluorescence staining by confocal microscope. The molecular mechanism of Lcn2 in bone marrow-derived macrophages (BMDMs) was analyzed by mass spectrometry (MS)-based quantitative proteomic analysis.Results: Compared to wild-type (WT) mice injected with LPS, Lcn2−/- mice injected with LPS showed increased inflammatory damage in jejunum and ileum, and significantly elevated the levels of multiple pro-inflammatory cytokines. After determining that Lcn2 was mainly located in the cytoplasm of macrophages, we isolated BMDMs from Lcn2−/- mice to evaluate their function. During LPS challenge, transcripts of pro-inflammatory cytokines were all significantly increased in BMDMs from Lcn2−/- mice, while those of anti-inflammatory cytokines were significantly decreased when compared with the cytokines in BMDMs from WT mice. A label-free relative quantitation proteomics analysis showed that LPS-treated BMDMs from Lcn2−/- mice had elevated levels of pro-inflammatory pathways, but reduced phagocytosis and autophagy when compared with LPS-treated BMDMs from WT mice.Conclusion: These findings demonstrated that Lcn2 was a potent protective factor in response to systemic inflammation and might be an indispensable factor for macrophage functions.Keywords: Lcn2, systemic inflammation, macrophages, BMDMs
format	article
author	Du H Liang L Li J Xiong Q Yu X Yu H
author_facet	Du H Liang L Li J Xiong Q Yu X Yu H
author_sort	Du H
title	Lipocalin-2 Alleviates LPS-Induced Inflammation Through Alteration of Macrophage Properties
title_short	Lipocalin-2 Alleviates LPS-Induced Inflammation Through Alteration of Macrophage Properties
title_full	Lipocalin-2 Alleviates LPS-Induced Inflammation Through Alteration of Macrophage Properties
title_fullStr	Lipocalin-2 Alleviates LPS-Induced Inflammation Through Alteration of Macrophage Properties
title_full_unstemmed	Lipocalin-2 Alleviates LPS-Induced Inflammation Through Alteration of Macrophage Properties
title_sort	lipocalin-2 alleviates lps-induced inflammation through alteration of macrophage properties
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/84ea15c760bc432a80d18f4cdb9aa1bc
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Lipocalin-2 Alleviates LPS-Induced Inflammation Through Alteration of Macrophage Properties

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