論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | CSII-EF-RfA (RDB04387) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394) |