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HIF1α-mediated TRAIL Expression Regulates Lacrimal Gland Inflammation in Dry Eye Disease

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dc.contributor.author서경률-
dc.contributor.author이형근-
dc.contributor.author강현구-
dc.contributor.author지용우-
dc.contributor.author최은영-
dc.contributor.author김현창-
dc.date.accessioned2020-09-28T00:52:02Z-
dc.date.available2020-09-28T00:52:02Z-
dc.date.issued2020-01-
dc.identifier.issn0146-0404-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/178966-
dc.description.abstractPurpose: The purpose of this study was to investigate the expression of death ligands in the lacrimal glands (LGs), identify upstream factors that regulate their expression, and determine the functional roles of these factors in the pathogenesis of dry eye disease (DED). Methods: For DED experiment, ex vivo coculture system with LG and in vivo murine model using a controlled environment chamber were utilized. C57BL/6 mice and hypoxia-inducible factor (HIF)-1α conditional knockout (CKO) mice were used. Immunohistochemical staining, polymerase chain reaction, and immunoblotting were performed to determine levels of death ligands including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in DED-induced LGs. Additionally, acinar cell and CD45+ cell apoptosis was determined with neutralizing TRAIL treatment. Results: Desiccating stress significantly increased HIF-1α expression in LG-acinar cells. Furthermore, HIF-1α deficiency significantly enhanced the infiltration of CD45+ inflammatory cells in LG and induced LG-acinar cell death. Meanwhile, only TRAIL expression was increased in DED-LG, but abrogated in HIF-1α CKO. Interestingly, the main source of TRAIL was the CD45- LG-acinar cells, but not CD45+ immune cells after DED induction. Using ex vivo coculture system, we confirmed LG-induced apoptosis of immune cells via HIF-1α-mediated TRAIL secretion following DED. Consistent with ex vivo, the insufficiency of HIF-1α and TRAIL enhanced recruitment of inflammatory cells to the LG and subsequently exacerbated ocular surface damage in DED mice. Conclusions: Our findings offer novel insight into the regulatory function of acinar cell-derived TRAIL in limiting inflammatory damage and could be implicated in the development of potential therapeutic strategies for DED.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherAssociation For Research In Vision And Ophthalmology (Arvo)-
dc.relation.isPartOfINVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAnimals-
dc.subject.MESHApoptosis-
dc.subject.MESHCoculture Techniques-
dc.subject.MESHDacryocystitis / metabolism*-
dc.subject.MESHDacryocystitis / pathology-
dc.subject.MESHDisease Models, Animal-
dc.subject.MESHDry Eye Syndromes / metabolism*-
dc.subject.MESHDry Eye Syndromes / pathology-
dc.subject.MESHEnzyme-Linked Immunosorbent Assay-
dc.subject.MESHFlow Cytometry-
dc.subject.MESHGene Expression Regulation / physiology*-
dc.subject.MESHHypoxia-Inducible Factor 1, alpha Subunit / physiology*-
dc.subject.MESHImmunoblotting-
dc.subject.MESHIn Situ Nick-End Labeling-
dc.subject.MESHLacrimal Apparatus / metabolism*-
dc.subject.MESHLacrimal Apparatus / pathology-
dc.subject.MESHMale-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred C57BL-
dc.subject.MESHMice, Knockout-
dc.subject.MESHOrgan Culture Techniques-
dc.subject.MESHReal-Time Polymerase Chain Reaction-
dc.subject.MESHTNF-Related Apoptosis-Inducing Ligand / genetics*-
dc.titleHIF1α-mediated TRAIL Expression Regulates Lacrimal Gland Inflammation in Dry Eye Disease-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Ophthalmology (안과학교실)-
dc.contributor.googleauthorYong Woo Ji-
dc.contributor.googleauthorJoon H Lee-
dc.contributor.googleauthorEun Young Choi-
dc.contributor.googleauthorHyun Goo Kang-
dc.contributor.googleauthorKyoung Yul Seo-
dc.contributor.googleauthorJong Suk Song-
dc.contributor.googleauthorHyeon Chang Kim-
dc.contributor.googleauthorHyung Keun Lee-
dc.identifier.doi10.1167/iovs.61.1.3-
dc.contributor.localIdA01870-
dc.contributor.localIdA03303-
dc.contributor.localIdA03303-
dc.contributor.localIdA04873-
dc.contributor.localIdA04873-
dc.contributor.localIdA03967-
dc.contributor.localIdA03967-
dc.contributor.localIdA05056-
dc.contributor.localIdA05056-
dc.contributor.localIdA01142-
dc.contributor.localIdA01142-
dc.relation.journalcodeJ01187-
dc.identifier.eissn1552-5783-
dc.identifier.pmid31995154-
dc.contributor.alternativeNameSeo, Kyoung Yul-
dc.contributor.affiliatedAuthor서경률-
dc.contributor.affiliatedAuthor이형근-
dc.contributor.affiliatedAuthor이형근-
dc.contributor.affiliatedAuthor강현구-
dc.contributor.affiliatedAuthor강현구-
dc.contributor.affiliatedAuthor지용우-
dc.contributor.affiliatedAuthor지용우-
dc.contributor.affiliatedAuthor최은영-
dc.contributor.affiliatedAuthor최은영-
dc.contributor.affiliatedAuthor김현창-
dc.contributor.affiliatedAuthor김현창-
dc.citation.volume61-
dc.citation.number1-
dc.citation.startPage3-
dc.identifier.bibliographicCitationINVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol.61(1) : 3, 2020-01-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Preventive Medicine (예방의학교실) > 1. Journal Papers

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