美国波士顿塔夫茨大学医学院Alexander Poltorak研究团队取得新进展。他们发现细胞FLICE样抑制蛋白（cFLIP）可通过抑制复合物II的形成来保护巨噬细胞免受LPS诱导的细胞焦亡。该研究于2020年3月20日发表于《科学》杂志上。

为了进一步表征脂多糖（LPS）诱导的体外分泌机制，他们揭示了cFLIP在调节炎症反应中的重要作用。

研究人员表示，细胞死亡和炎症是宿主对感染的相互依赖反应。在细胞焦亡期间，白细胞介素1β（IL-1β）通过caspase-1和caspase-11介导形成的gasdermin D孔释放。在体内，对LPS的反应导致IL-1β分泌。然而，在体外，鼠巨噬细胞需要炎性体驱动的IL-1β成熟的第二个“危险信号”。最近的报道显示，在LPS活化的巨噬细胞中，caspase-8介导细胞焦亡，但在这些条件下有关IL-1β释放的证据相互矛盾。

附：英文原文

Title: cFLIPL protects macrophages from LPS-induced pyroptosis via inhibition of complex II formation

Author: Hayley I. Muendlein, David Jetton, Wilson M. Connolly, Keith P. Eidell, Zoie Magri, Irina Smirnova, Alexander Poltorak

Issue&Volume: 2020/03/20

Abstract: Abstract

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.

DOI: 10.1126/science.aay3878

Source: https://science.sciencemag.org/content/367/6484/1379