CFLIP_S regulates alternative NLRP3 inflammasome activation in human monocytes.

ABSTRACT: The innate immune responses, including inflammasome activation, are paramount for host defense against pathogen infection. In contrast to canonical and noncanonical inflammasome activation, in this study, heat-killed gram-negative bacteria (HK bacteria) were identified as single-step stimulators of the NLRP3 inflammasome in human monocytes, and they caused a moderate amount of IL-1β to be released from cells. Time course experiments showed that this alternative inflammasome response was finished within a few hours. Further analysis showed that the intrinsically limited NLRP3 inflammasome activation response was due to the negative regulation of caspase-8 by the short isoform of cFLIP (cFLIPs), which was activated by NF-κB. In contrast, overexpressed cFLIP_S, but not overexpressed

SUBMITTER: Gao Y 

PROVIDER: S-EPMC10541859 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature