327,299 research outputs found

    Participation of c-FLIP in NLRP3 and AIM2 inflammasome activation

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    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

    Kuo-2014-Genetics-Fig3

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    These primary data are summarized and discussed in Kuo et al., Genetics (2014). Data in this file are from the P{wa} assay, first published in Adams et al., Science (2002), DOI: 10.1126/science.1077198 . The first tab has counts of progeny from each vial. As in other uses of this assay, only daughters that did not recieve the transposase chromosome (Cy+) were scored. Since the Df(3R)ED6058 chromosome has w+ on it, only progeny that recieved a Sbchromosome were scored. f red = frequency of red-eyed flies f yellow = frequency of yellow-eyed flies The last tab has molecular analysis of synthesis and/or deletion in the yellow-eyed daughters. Each row represents presence (+) or absence (-) of a PCR product in white-eyed sons of yellow-eyed progeny. Each yellow-eyed progeny came from a different vials (f numbers are Fancm, c numbers are control). Distance of furthers primer from left or right end of the element is indicated. Primers used are listed

    Kuo, Ni W.

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    Se-Kuo Church

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    Se-Kuo Church. China. B/W Photo.https://digitalcommons.whitworth.edu/cmh_friars_minor/1057/thumbnail.jp
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