| RRC ID |
31341
|
| Author |
Liu T, Yamaguchi Y, Shirasaki Y, Shikada K, Yamagishi M, Hoshino K, Kaisho T, Takemoto K, Suzuki T, Kuranaga E, Ohara O, Miura M.
|
| Title |
Single-cell imaging of caspase-1 dynamics reveals an all-or-none inflammasome signaling response.
|
| Journal |
Cell Rep
|
| Abstract |
Inflammasome-mediated caspase-1 activation is involved in cell death and the secretion of the proinflammatory cytokine interleukin-1β (IL-1β). Although the dynamics of caspase-1 activation, IL-1β 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-1β release demonstrated that dead macrophages containing activated caspase-1 release a local burst of IL-1β in a digital manner, which identified these macrophages as the main source of IL-1β within cell populations. Our results highlight the value of single-cell analysis in enhancing understanding of the inflammasome system and chronic inflammatory diseases.
|
| Volume |
8(4)
|
| Pages |
974-82
|
| Published |
2014-8-21
|
| DOI |
10.1016/j.celrep.2014.07.012
|
| PII |
S2211-1247(14)00579-8
|
| PMID |
25127135
|
| MeSH |
Animals
Caspase 1 / physiology*
Cells, Cultured
Enzyme Activation
Humans
Inflammasomes / metabolism*
Interleukin-1beta / physiology
Kinetics
Lipopolysaccharides / pharmacology
Macrophages, Peritoneal / enzymology
Macrophages, Peritoneal / immunology
Mice, Transgenic
Signal Transduction
Single-Cell Analysis
|
| IF |
8.109
|
| Times Cited |
81
|
|
WOS Category
|
CELL BIOLOGY
|
| Resource |
| Mice |
RBRC01828 |
