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Publication : Single-cell imaging of caspase-1 dynamics reveals an all-or-none inflammasome signaling response.

First Author  Liu T Year  2014
Journal  Cell Rep Volume  8
Issue  4 Pages  974-82
PubMed ID  25127135 Mgi Jnum  J:297265
Mgi Id  MGI:6148093 Doi  10.1016/j.celrep.2014.07.012
Citation  Liu T, et al. (2014) Single-cell imaging of caspase-1 dynamics reveals an all-or-none inflammasome signaling response. Cell Rep 8(4):974-82
abstractText  Inflammasome-mediated caspase-1 activation is involved in cell death and the secretion of the proinflammatory cytokine interleukin-1beta (IL-1beta). Although the dynamics of caspase-1 activation, IL-1beta secretion, and cell death have been examined with bulk assays in population-level studies, they remain poorly understood at the single-cell level. In this study, we conducted single-cell imaging using a genetic fluorescence resonance energy transfer sensor that detects caspase-1 activation. We determined that caspase-1 exhibits all-or-none (digital) activation at the single-cell level, with similar activation kinetics irrespective of the type of inflammasome or the intensity of the stimulus. Real-time concurrent detection of caspase-1 activation and IL-1beta release demonstrated that dead macrophages containing activated caspase-1 release a local burst of IL-1beta in a digital manner, which identified these macrophages as the main source of IL-1beta within cell populations. Our results highlight the value of single-cell analysis in enhancing understanding of the inflammasome system and chronic inflammatory diseases.
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