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Autophagy induced by AXL receptor tyrosine kinase alleviates acute liver injury via inhibition of NLRP3 inflammasome activation in mice

DC FieldValueLanguage
dc.contributor.author이명식-
dc.date.accessioned2018-11-06T16:40:07Z-
dc.date.available2018-11-06T16:40:07Z-
dc.date.issued2016-
dc.identifier.issn1554-8627-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/165064-
dc.description.abstractSevere hepatic inflammation is a common cause of acute or chronic liver disease. Macrophages are one of the key mediators which regulate the progress of hepatic inflammation. Increasing evidence shows that the TAM (TYRO3, AXL and MERTK) family of RTKs (receptor tyrosine kinases), which is expressed in macrophages, alleviates inflammatory responses through a negative feedback loop. However, the functional contribution of each TAM family member to the progression of hepatic inflammation remains elusive. In this study, we explore the role of individual TAM family proteins during autophagy induction and evaluate their contribution to hepatic inflammation. Among the TAM family of RTKs, AXL (AXL receptor tyrosine kinase) only induces autophagy in macrophages after interaction with its ligand, GAS6 (growth arrest specific 6). Based on our results, autophosphorylation of 2 tyrosine residues (Tyr815 and Tyr860) in the cytoplasmic domain of AXL in mice is required for autophagy induction and AXL-mediated autophagy induction is dependent on MAPK (mitogen-activated protein kinase)14 activity. Furthermore, induction of AXL-mediated autophagy prevents CASP1 (caspase 1)-dependent IL1B (interleukin 1, β) and IL18 (interleukin 18) maturation by inhibiting NLRP3 (NLR family, pyrin domain containing 3) inflammasome activation. In agreement with these observations, axl-/- mice show more severe symptoms than do wild-type (Axl+/+) mice following acute hepatic injury induced by administration of lipopolysaccharide (LPS) or carbon tetrachloride (CCl4). Hence, GAS6-AXL signaling-mediated autophagy induction in murine macrophages ameliorates hepatic inflammatory responses by inhibiting NLRP3 inflammasome activation.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherTaylor & Francis-
dc.relation.isPartOfAutophagy-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHAutophagy*-
dc.subject.MESHAutophagy-Related Protein 5/genetics-
dc.subject.MESHAutophagy-Related Protein 5/metabolism-
dc.subject.MESHBeclin-1/genetics-
dc.subject.MESHBeclin-1/metabolism-
dc.subject.MESHInflammasomes/metabolism*-
dc.subject.MESHIntercellular Signaling Peptides and Proteins/metabolism-
dc.subject.MESHInterleukin-18/biosynthesis-
dc.subject.MESHInterleukin-1beta/biosynthesis-
dc.subject.MESHKupffer Cells/metabolism-
dc.subject.MESHKupffer Cells/pathology-
dc.subject.MESHLiver/enzymology-
dc.subject.MESHLiver/injuries*-
dc.subject.MESHLiver/pathology*-
dc.subject.MESHMacrophages/enzymology-
dc.subject.MESHMacrophages/pathology-
dc.subject.MESHMice-
dc.subject.MESHMicrotubule-Associated Proteins/genetics-
dc.subject.MESHMicrotubule-Associated Proteins/metabolism-
dc.subject.MESHMitogen-Activated Protein Kinase 14/metabolism-
dc.subject.MESHModels, Biological-
dc.subject.MESHNLR Family, Pyrin Domain-Containing 3 Protein/metabolism*-
dc.subject.MESHPhosphorylation-
dc.subject.MESHProtein Binding-
dc.subject.MESHProtein Domains-
dc.subject.MESHProto-Oncogene Proteins/chemistry-
dc.subject.MESHProto-Oncogene Proteins/deficiency-
dc.subject.MESHProto-Oncogene Proteins/metabolism*-
dc.subject.MESHRNA, Messenger/genetics-
dc.subject.MESHRNA, Messenger/metabolism-
dc.subject.MESHReceptor Protein-Tyrosine Kinases/chemistry-
dc.subject.MESHReceptor Protein-Tyrosine Kinases/deficiency-
dc.subject.MESHReceptor Protein-Tyrosine Kinases/metabolism*-
dc.subject.MESHSignal Transduction-
dc.titleAutophagy induced by AXL receptor tyrosine kinase alleviates acute liver injury via inhibition of NLRP3 inflammasome activation in mice-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentBioMedical Science Institute (의생명과학부)-
dc.contributor.googleauthorJihye Han-
dc.contributor.googleauthorJoonbeom Bae-
dc.contributor.googleauthorChang-Yong Choi-
dc.contributor.googleauthorSang-Pil Choi-
dc.contributor.googleauthorHyung-Sik Kang-
dc.contributor.googleauthorEun-Kyeong Jo-
dc.contributor.googleauthorJongsun Park-
dc.contributor.googleauthorYoung Sik Lee-
dc.contributor.googleauthorHyun-Seuk Moon-
dc.contributor.googleauthorChung-Gyu Park-
dc.contributor.googleauthorMyung-Shik Lee-
dc.contributor.googleauthorTaehoon Chun-
dc.identifier.doi10.1080/15548627.2016.1235124-
dc.contributor.localIdA02752-
dc.contributor.localIdA02752-
dc.relation.journalcodeJ00269-
dc.identifier.eissn1554-8635-
dc.identifier.pmid27780404-
dc.subject.keywordAXL receptor tyrosine kinase-
dc.subject.keywordNLRP3 inflammasome-
dc.subject.keywordautophagy-
dc.subject.keywordhepatic inflammation-
dc.subject.keywordmacrophage-
dc.contributor.alternativeNameLee, Myung Shik-
dc.contributor.affiliatedAuthor이명식-
dc.citation.volume12-
dc.citation.number12-
dc.citation.startPage2326-
dc.citation.endPage2343-
dc.identifier.bibliographicCitationAutophagy, Vol.12(12) : 2326-2343, 2016-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers

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