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Interferon gamma (IFNgamma ) and tumor necrosis factor alpha synergism in ME-180 cervical cancer cell apoptosis and necrosis. IFNgamma inhibits cytoprotective NF-kappa B through STAT1/IRF-1 pathways

DC FieldValueLanguage
dc.contributor.author장인익-
dc.date.accessioned2016-02-19T11:29:00Z-
dc.date.available2016-02-19T11:29:00Z-
dc.date.issued2001-
dc.identifier.issn0021-9258-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/143239-
dc.description.abstractWe investigated the molecular mechanism of the synergism between interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) documented in a variety of biological occasions such as tumor cell death and inflammatory responses. IFNgamma/TNFalpha synergistically induced apoptosis of ME-180 cervical cancer cells. IFNgamma induced STAT1 phosphorylation and interferon regulatory factor 1 (IRF-1) expression. Transfection of phosphorylation-defective STAT1 inhibited IFNgamma/TNFalpha-induced apoptosis, whereas IRF-1 transfection induced susceptibility to TNFalpha. Dominant-negative IkappaBalpha transfection sensitized ME-180 cells to TNFalpha. IFNgamma pretreatment attenuated TNFalpha- or p65-induced NF-kappaB reporter activity, whereas it did not inhibit p65 translocation or DNA binding of NF-kappaB. IRF-1 transfection alone inhibited TNFalpha-induced NF-kappaB activity, which was reversed by coactivator p300 overexpression. Caspases were activated by IFNgamma/TNFalpha combination; however, caspase inhibition did not abrogate IFNgamma/TNFalpha-induced cell death. Instead, caspase inhibitors directed IFNgamma/TNFalpha-treated ME-180 cells to undergo necrosis, as demonstrated by Hoechst 33258/propidium iodide staining and electron microscopy. Taken together, our results indicate that IFNgamma and TNFalpha synergistically act to destroy ME-180 tumor cells by either apoptosis or necrosis, depending on caspase activation, and STAT1/IRF-1 pathways initiated by IFNgamma play a critical role in IFNgamma/TNFalpha synergism by inhibiting cytoprotective NF-kappaB. IFNgamma/TNFalpha synergism appears to activate cell death machinery independently of caspase activation, and caspase activation seems to merely determine the mode of cell death.-
dc.description.statementOfResponsibilityopen-
dc.format.extent13153~13159-
dc.relation.isPartOfJOURNAL OF BIOLOGICAL CHEMISTRY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHApoptosis/drug effects*-
dc.subject.MESHCaspase 3-
dc.subject.MESHCaspase 8-
dc.subject.MESHCaspase 9-
dc.subject.MESHCaspases/metabolism-
dc.subject.MESHCell Survival/drug effects-
dc.subject.MESHCysteine Proteinase Inhibitors/pharmacology-
dc.subject.MESHDNA-Binding Proteins/metabolism*-
dc.subject.MESHDrug Synergism-
dc.subject.MESHFemale-
dc.subject.MESHHumans-
dc.subject.MESHInterferon Regulatory Factor-1-
dc.subject.MESHInterferon-gamma/toxicity*-
dc.subject.MESHNF-kappa B/metabolism*-
dc.subject.MESHNecrosis-
dc.subject.MESHPhosphoproteins/metabolism*-
dc.subject.MESHPloidies-
dc.subject.MESHRecombinant Proteins/metabolism-
dc.subject.MESHRecombinant Proteins/toxicity-
dc.subject.MESHSTAT1 Transcription Factor-
dc.subject.MESHTrans-Activators/metabolism*-
dc.subject.MESHTranscription Factors/metabolism-
dc.subject.MESHTransfection-
dc.subject.MESHTumor Cells, Cultured-
dc.subject.MESHTumor Necrosis Factor-alpha/toxicity*-
dc.subject.MESHUterine Cervical Neoplasms/pathology-
dc.titleInterferon gamma (IFNgamma ) and tumor necrosis factor alpha synergism in ME-180 cervical cancer cell apoptosis and necrosis. IFNgamma inhibits cytoprotective NF-kappa B through STAT1/IRF-1 pathways-
dc.typeArticle-
dc.contributor.collegeCollege of Dentistry (치과대학)-
dc.contributor.departmentDept. of Oral Biology (구강생물학)-
dc.contributor.googleauthorKyoungho Suk-
dc.contributor.googleauthorInik Chang-
dc.contributor.googleauthorYun-Hee Kim-
dc.contributor.googleauthorSunshin Kim-
dc.contributor.googleauthorJa Young Kim-
dc.contributor.googleauthorHocheol Kim-
dc.contributor.googleauthorMyung-Shik Lee-
dc.identifier.doi10.1074/jbc.M007646200-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03461-
dc.relation.journalcodeJ01258-
dc.identifier.eissn1083-351X-
dc.identifier.pmid11278357-
dc.identifier.urlhttp://www.jbc.org/content/276/16/13153.long-
dc.contributor.alternativeNameChang, In Ik-
dc.contributor.affiliatedAuthorChang, In Ik-
dc.rights.accessRightsfree-
dc.citation.volume276-
dc.citation.number16-
dc.citation.startPage13153-
dc.citation.endPage13159-
dc.identifier.bibliographicCitationJOURNAL OF BIOLOGICAL CHEMISTRY, Vol.276(16) : 13153-13159, 2001-
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers

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