气候变化领域集成服务门户(CCPortal): CFLIPL protects macrophages from LPS-induced pyroptosis via inhibition of complex II formation

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DOI	10.1126/science.aay3878
	CFLIPL protects macrophages from LPS-induced pyroptosis via inhibition of complex II formation
	Muendlein H.I.; Jetton D.; Connolly W.M.; Eidell K.P.; Magri Z.; Smirnova I.; Poltorak A.
发表日期	2020
ISSN	0036-8075
起始页码	1379
结束页码	1384
卷号	367 期号:6484
英文摘要	Cell death and inflammation are interdependent host responses to infection. During pyroptotic cell death, interleukin-1β (IL-1β) release occurs through caspase-1 and caspase-11-mediated gasdermin D pore formation. In vivo, responses to lipopolysaccharide (LPS) result in IL-1β secretion. In vitro, however, murine macrophages require a second “danger signal” for the inflammasome-driven maturation of IL-1β. Recent reports have shown caspase-8-mediated pyroptosis in LPS-activated macrophages but have provided conflicting evidence regarding the release of IL-1β under these conditions. Here, to further characterize the mechanism of LPS-induced secretion in vitro, we reveal an important role for cellular FLICE-like inhibitory protein (cFLIP) in the regulation of the inflammatory response. Specifically, we show that deficiency of the long isoform cFLIPL promotes complex II formation, driving pyroptosis, and the secretion of IL-1β in response to LPS alone. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词	FLICE inhibitory protein interleukin 1beta lipopolysaccharide messenger RNA succinate dehydrogenase (ubiquinone)Casp1 protein, mouse caspase 8 Cflar protein, mouse cryopyrin FLICE inhibitory protein IL1B protein, mouse inflammasome interleukin 1beta interleukin 1beta converting enzyme lipopolysaccharide succinate dehydrogenase (ubiquinone)cell enzyme activity inhibition maturation protein animal cell animal experiment Article bone marrow derived macrophage cell death cell protection complex formation controlled study cytokine release in vitro study inflammation mouse nonhuman priority journal protein analysis protein degradation protein function protein interaction pyroptosis animal gene knockdown genetics immunology macrophage macrophage activation metabolism physiology Murinae Animals CASP8 and FADD-Like Apoptosis Regulating Protein Caspase 1 Caspase 8 Electron Transport Complex II Gene Knockdown Techniques Inflammasomes Interleukin-1beta Lipopolysaccharides Macrophage Activation Macrophages Mice NLR Family, Pyrin Domain-Containing 3 Protein Pyroptosis
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133621
推荐引用方式 GB/T 7714	Muendlein H.I.,Jetton D.,Connolly W.M.,et al. CFLIPL protects macrophages from LPS-induced pyroptosis via inhibition of complex II formation[J]. Science,2020,367(6484).
APA	Muendlein H.I..,Jetton D..,Connolly W.M..,Eidell K.P..,Magri Z..,...&Poltorak A..(2020).CFLIPL protects macrophages from LPS-induced pyroptosis via inhibition of complex II formation.,367(6484).
MLA	Muendlein H.I.,et al."CFLIPL protects macrophages from LPS-induced pyroptosis via inhibition of complex II formation".367.6484(2020).