https://scholars.lib.ntu.edu.tw/handle/123456789/160874
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor | 臺大醫學院-免疫學研究所; | - |
dc.contributor.author | Wu, Y-H | en |
dc.contributor.author | Kuo, W-C | en |
dc.contributor.author | Wu, Y-J | en |
dc.contributor.author | Yang, K-T | en |
dc.contributor.author | Chen, S-T | en |
dc.contributor.author | Jiang, S-T | en |
dc.contributor.author | Gordy, C. | en |
dc.contributor.author | He, Y-W | en |
dc.contributor.author | Lai, M-Z | en |
dc.creator | Wu, Y-H;Kuo, W-C;Wu, Y-J;Yang, K-T;Chen, S-T;Jiang, S-T;Gordy, C.;He, Y-W;Lai, M-Z | en |
dc.creator | 賴明宗 | zh-tw |
dc.date | 2014 | - |
dc.date.accessioned | 2017-05-25T05:22:27Z | - |
dc.date.accessioned | 2018-07-09T01:57:50Z | - |
dc.date.available | 2017-05-25T05:22:27Z | - |
dc.date.available | 2018-07-09T01:57:50Z | - |
dc.date.issued | 2014 | - |
dc.identifier.uri | http://ntur.lib.ntu.edu.tw//handle/246246/278900 | - |
dc.description.abstract | Cellular FLICE-inhibitory protein (c-FLIP) is an inhibitor of caspase-8 and is required for macrophage survival. Recent studies have revealed a selective role of caspase-8 in noncanonical IL-1 beta production that is independent of caspase-1 or inflammasome. Here we demonstrated that c-FLIPL is an unexpected contributor to canonical inflammasome activation for the generation of caspase-1 and active IL-1 beta. Hemizygotic deletion of c-FLIP impaired ATP-and monosodium uric acid (MSU)-induced IL-1 beta production in macrophages primed through Toll-like receptors (TLRs). Decreased IL-1 beta expression was attributed to a reduced activation of caspase-1 in c-FLIP hemizygotic cells. In contrast, the production of TNF-alpha was not affected by downregulation in c-FLIP. c-FLIPL interacted with NLRP3 or procaspase-1. c-FLIP is required for the full NLRP3 inflammasome assembly and NLRP3 mitochondrial localization, and c-FLIP is associated with NLRP3 inflammasome. c-FLIP downregulation also reduced AIM2 inflammasome activation. In contrast, c-FLIP inhibited SMAC mimetic-, FasL-, or Dectin-1-induced IL-1 beta generation that is caspase-8-mediated. Our results demonstrate a prominent role of c-FLIPL in the optimal activation of the NLRP3 and AIM2 inflammasomes, and suggest that c-FLIP could be a valid target for treatment of inflammatory diseases caused by over-activation of inflammasomes. | - |
dc.language | en-us | - |
dc.relation | Cell Death Differ., 21(3), 451-461 | - |
dc.relation.ispartof | Cell Death and Differentiation | en_US |
dc.subject | c-FLIP | - |
dc.subject | inflammasome | - |
dc.subject | IL-1 beta | - |
dc.subject | caspase-1 | - |
dc.subject | caspase-8 | - |
dc.subject | macrophages | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | AIM2 protein, human; Aim2 protein, mouse; carrier protein; CIAS1 protein, mouse; DNA binding protein; FLICE inhibitory protein; inflammasome; interleukin 1beta; NLRP3 protein, human; peptide; transfecting peptide I; animal; down regulation; genetics; HEK293 cell line; human; macrophage; metabolism; mouse; signal transduction; Animals; Carrier Proteins; CASP8 and FADD-Like Apoptosis Regulating Protein; DNA-Binding Proteins; Down-Regulation; HEK293 Cells; Humans; Inflammasomes; Interleukin-1beta; Macrophages; Mice; Peptides; Signal Transduction | - |
dc.title | Participation of c-FLIP in NLRP3 and AIM2 inflammasome activation | - |
dc.identifier.doi | 10.1038/cdd.2013.165 | - |
dc.relation.pages | 451-461 | - |
item.fulltext | no fulltext | - |
item.grantfulltext | none | - |
顯示於: | 免疫學研究所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。