Abstract
Inflammation plays a critical role in initiation of adaptive immunity, pathogen clearance and tissue repair. Interleukin (IL)-1β is a potent pro-inflammatory cytokine and therefore its production is tightly regulated: its secretion requires the assembly of a macromolecular protein complex, termed the inflammasome. Aberrant activation of the inflammasome has been linked to debilitating human diseases including chronic inflammatory and autoimmune diseases. Thus, there is a great interest in understanding how inflammasomes are regulated. Here we show that Dicer, an enzyme necessary for the production of mature micro-RNAs (miRNAs), is required for optimal activation of NLRP3 inflammasomes in bone marrow macrophages. Our data indicate that miRNAs may play an important role in promoting inflammasome activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cells, Cultured
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Computational Biology
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DEAD-box RNA Helicases / genetics
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DEAD-box RNA Helicases / metabolism*
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation / immunology
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Immunity, Innate / genetics*
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Inflammasomes / immunology*
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Inflammasomes / metabolism
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Macrophages
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Mice
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Mice, Transgenic
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MicroRNAs / metabolism*
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NLR Family, Pyrin Domain-Containing 3 Protein / immunology
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NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
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Primary Cell Culture
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Ribonuclease III / genetics
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Ribonuclease III / metabolism*
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Signal Transduction / genetics
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Up-Regulation
Substances
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Aim2 protein, mouse
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DNA-Binding Proteins
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Inflammasomes
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MicroRNAs
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NLR Family, Pyrin Domain-Containing 3 Protein
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Nlrp3 protein, mouse
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Dicer1 protein, mouse
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Ribonuclease III
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DEAD-box RNA Helicases
Grants and funding
This work was funded by York University startup funds to AA-S and the Alpha Foundation to DMO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.