| RRC ID |
61361
|
| 著者 |
Seki R, Ohta A, Niwa A, Sugimine Y, Naito H, Nakahata T, Saito MK.
|
| タイトル |
Induced pluripotent stem cell-derived monocytic cell lines from a NOMID patient serve as a screening platform for modulating NLRP3 inflammasome activity.
|
| ジャーナル |
PLoS One
|
| Abstract |
Curative therapeutic options for a number of immunological disorders remain to be established, and approaches for identifying drug candidates are relatively limited. Furthermore, phenotypic screening methods using induced pluripotent stem cell (iPSC)-derived immune cells or hematopoietic cells need improvement. In the present study, using immortalized monocytic cell lines derived from iPSCs, we developed a high-throughput screening (HTS) system to detect compounds that inhibit IL-1β secretion and NLRP3 inflammasome activation from activated macrophages. The iPSCs were generated from a patient with neonatal onset multisystem inflammatory disease (NOMID) as a model of a constitutively activated NLRP3 inflammasome. HTS of 4,825 compounds including FDA-approved drugs and compounds with known bioactivity identified 7 compounds as predominantly IL-1β inhibitors. Since these compounds are known inflammasome inhibitors or derivatives of, these results prove the validity of our HTS system, which can be a versatile platform for identifying drug candidates for immunological disorders associated with monocytic lineage cells.
|
| 巻・号 |
15(8)
|
| ページ |
e0237030
|
| 公開日 |
2020-1-1
|
| DOI |
10.1371/journal.pone.0237030
|
| PII |
PONE-D-20-09012
|
| PMID |
32810141
|
| PMC |
PMC7437452
|
| MeSH |
Carrier Proteins / metabolism
Caspase 1 / metabolism
Cell Line
Cells, Cultured
Cryopyrin-Associated Periodic Syndromes / immunology
Cryopyrin-Associated Periodic Syndromes / physiopathology
High-Throughput Screening Assays / methods*
Humans
Induced Pluripotent Stem Cells / metabolism
Inflammasomes / metabolism*
Inflammasomes / physiology
Inflammation / metabolism
Interleukin-1beta
Macrophages / metabolism
Monocytes / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
NLR Family, Pyrin Domain-Containing 3 Protein / physiology
|
| IF |
2.74
|
| リソース情報 |
| 遺伝子材料 |
CSII-EF-RfA (RDB04387)
pCMV-VSV-G-RSV-Rev (RDB04393)
pCAG-HIVgp (RDB04394) |
