File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Lipocalin-2 Mediates Non-alcoholic Steatohepatitis by Promoting Neutrophil-Macrophage Crosstalk via The Induction of CXCR2

TitleLipocalin-2 Mediates Non-alcoholic Steatohepatitis by Promoting Neutrophil-Macrophage Crosstalk via The Induction of CXCR2
Authors
Issue Date2016
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep
Citation
Journal of Hepatology, 2016 How to Cite?
AbstractBACKGROUND & AIMS: Inflammatory cell infiltration in the liver is a hallmark of nonalcoholic steatohepatitis (NASH). However, the pathological events which trigger the infiltration of inflammatory cells to mediate NASH pathogenesis remains poorly understood. This study aims to investigate the role of neutrophil-derived lipocalin 2 (LCN2) in mediating the transition from simple steatosis to NASH. METHODS: Animal models of NASH were induced by high fat high cholesterol (HFHC) diet and methionine- and choline-deficient (MCD) diet in LCN2 knockout mice and wild type controls. RESULTS: Circulating levels of LCN2 and its hepatic expression were markedly increased in both murine models and human subjects with NASH, and these changes were associated with increased infiltration of neutrophils. In diet-induced NASH models, hepatic injury, neoinflammation and infiltration of neutrophils and macrophages were substantially attenuated by genetic depletion of LCN2. In contrast, chronic infusion of recombinant LCN2 exacerbated diet-induced liver injury, inflammation and macrophage accumulation in a neutrophil-dependent manner. Primary mouse neutrophils lacking LCN2 exhibited a defective migration capacity, which can be reversed by replenishment with recombinant LCN2. Mechanistically, LCN2 induced the expression of the chemokine (C-X-C motif) receptor 2 (CXCR2), thereby leading to activation of ERK1/2 and production of pro-inflammatory chemokines. LCN2-induced inflammation, infiltration of macrophages and liver injury was abrogated in CXCR2-deficient mice. CONCLUSIONS: These findings demonstrated that LCN2 acts as a central mediator to facilitate the crosstalk between neutrophils and hepatic macrophages via induction of the chemokine receptor CXCR2, thereby exacerbating steatohepatitis
Persistent Identifierhttp://hdl.handle.net/10722/229383
ISSN
2015 Impact Factor: 10.59
2015 SCImago Journal Rankings: 4.570

 

DC FieldValueLanguage
dc.contributor.authorYe, D-
dc.contributor.authorYang, KANGMIN-
dc.contributor.authorChau, HAU TAK-
dc.contributor.authorXu, A-
dc.contributor.authorWang, Y-
dc.date.accessioned2016-08-23T14:10:49Z-
dc.date.available2016-08-23T14:10:49Z-
dc.date.issued2016-
dc.identifier.citationJournal of Hepatology, 2016-
dc.identifier.issn0168-8278-
dc.identifier.urihttp://hdl.handle.net/10722/229383-
dc.description.abstractBACKGROUND & AIMS: Inflammatory cell infiltration in the liver is a hallmark of nonalcoholic steatohepatitis (NASH). However, the pathological events which trigger the infiltration of inflammatory cells to mediate NASH pathogenesis remains poorly understood. This study aims to investigate the role of neutrophil-derived lipocalin 2 (LCN2) in mediating the transition from simple steatosis to NASH. METHODS: Animal models of NASH were induced by high fat high cholesterol (HFHC) diet and methionine- and choline-deficient (MCD) diet in LCN2 knockout mice and wild type controls. RESULTS: Circulating levels of LCN2 and its hepatic expression were markedly increased in both murine models and human subjects with NASH, and these changes were associated with increased infiltration of neutrophils. In diet-induced NASH models, hepatic injury, neoinflammation and infiltration of neutrophils and macrophages were substantially attenuated by genetic depletion of LCN2. In contrast, chronic infusion of recombinant LCN2 exacerbated diet-induced liver injury, inflammation and macrophage accumulation in a neutrophil-dependent manner. Primary mouse neutrophils lacking LCN2 exhibited a defective migration capacity, which can be reversed by replenishment with recombinant LCN2. Mechanistically, LCN2 induced the expression of the chemokine (C-X-C motif) receptor 2 (CXCR2), thereby leading to activation of ERK1/2 and production of pro-inflammatory chemokines. LCN2-induced inflammation, infiltration of macrophages and liver injury was abrogated in CXCR2-deficient mice. CONCLUSIONS: These findings demonstrated that LCN2 acts as a central mediator to facilitate the crosstalk between neutrophils and hepatic macrophages via induction of the chemokine receptor CXCR2, thereby exacerbating steatohepatitis-
dc.languageeng-
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep-
dc.relation.ispartofJournal of Hepatology-
dc.rightsPosting accepted manuscript (postprint): © <year>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.titleLipocalin-2 Mediates Non-alcoholic Steatohepatitis by Promoting Neutrophil-Macrophage Crosstalk via The Induction of CXCR2-
dc.typeArticle-
dc.identifier.emailYe, D: deweiye@hku.hk-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.emailWang, Y: yuwanghk@hku.hk-
dc.identifier.authorityXu, A=rp00485-
dc.identifier.authorityWang, Y=rp00239-
dc.identifier.doi10.1016/j.jhep.2016.05.041-
dc.identifier.pmid27266617-
dc.identifier.hkuros261775-
dc.publisher.placeNetherlands-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats