Induced pluripotent stem cell-derived monocytic cell lines from a NOMID patient serve as a screening platform for modulating NLRP3 inflammasome activity

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...

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Published in:PloS one 2020-08, Vol.15 (8), p.e0237030-e0237030
Main Authors: Seki, Ryosuke, Ohta, Akira, Niwa, Akira, Sugimine, Yoshinori, Naito, Haruna, Nakahata, Tatsutoshi, Saito, Megumu K
Format: Article
Language:English
Subjects:
Biological activity
Biology and Life Sciences
Biotechnology
Care and treatment
Carrier Proteins - metabolism
Caspase 1 - metabolism
Cell activation
Cell Line
Cell lines
Cells, Cultured
Cloning
Cryopyrin-Associated Periodic Syndromes - immunology
Cryopyrin-Associated Periodic Syndromes - physiopathology
Cytokines
Diagnosis
Disease
Disorders
Drug development
Genotype & phenotype
Health aspects
High-throughput screening
High-Throughput Screening Assays - methods
Humans
Identification methods
IL-1β
Immune system
Immunologic diseases
Immunology
Immunosuppressive agents
Induced Pluripotent Stem Cells - metabolism
Inflammasomes
Inflammasomes - metabolism
Inflammasomes - physiology
Inflammation - metabolism
Inflammatory diseases
Inhibitors
Inhibitory postsynaptic potentials
Interleukin-1beta
Macrophages
Macrophages - metabolism
Medicine and Health Sciences
Monocytes
Monocytes - metabolism
Mutation
Neonatal diseases
Neonates
NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
NLR Family, Pyrin Domain-Containing 3 Protein - physiology
Patients
Pluripotency
Screening
Signal transduction
Stem cells
Supervision
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cited_by cdi_FETCH-LOGICAL-c692t-a3de410bfc220c031f2e2f237c2eb2ffee106b3b33e352b83143d4066486e7843
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container_end_page e0237030
container_issue 8
container_start_page e0237030
container_title PloS one
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creator Seki, Ryosuke
Ohta, Akira
Niwa, Akira
Sugimine, Yoshinori
Naito, Haruna
Nakahata, Tatsutoshi
Saito, Megumu K
description 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.
doi_str_mv 10.1371/journal.pone.0237030
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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. 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source Open Access: PubMed Central; Publicly Available Content Database
subjects Biological activity
Biology and Life Sciences
Biotechnology
Care and treatment
Carrier Proteins - metabolism
Caspase 1 - metabolism
Cell activation
Cell Line
Cell lines
Cells, Cultured
Cloning
Cryopyrin-Associated Periodic Syndromes - immunology
Cryopyrin-Associated Periodic Syndromes - physiopathology
Cytokines
Diagnosis
Disease
Disorders
Drug development
Genotype & phenotype
Health aspects
High-throughput screening
High-Throughput Screening Assays - methods
Humans
Identification methods
IL-1β
Immune system
Immunologic diseases
Immunology
Immunosuppressive agents
Induced Pluripotent Stem Cells - metabolism
Inflammasomes
Inflammasomes - metabolism
Inflammasomes - physiology
Inflammation - metabolism
Inflammatory diseases
Inhibitors
Inhibitory postsynaptic potentials
Interleukin-1beta
Macrophages
Macrophages - metabolism
Medicine and Health Sciences
Monocytes
Monocytes - metabolism
Mutation
Neonatal diseases
Neonates
NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
NLR Family, Pyrin Domain-Containing 3 Protein - physiology
Patients
Pluripotency
Screening
Signal transduction
Stem cells
Supervision
title Induced pluripotent stem cell-derived monocytic cell lines from a NOMID patient serve as a screening platform for modulating NLRP3 inflammasome activity
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