Abstract
Lipocalin-2 (LCN2), a small secretory glycoprotein, is upregulated by toll-like receptor (TLR) signaling in various cells and tissues. LCN2 inhibits bacterial growth by iron sequestration and regulates the innate immune system. Inflammasome activates the inflammatory caspases leading to pyroptosis and cytokine maturation. This study examined the effects of inflammasome activation on LCN2 secretion in response to TLR signaling. The triggers of NLRP3 inflammasome activation attenuated LCN2 secretion while it induced interleukin-1β in mouse macrophages. In mice, NLRP3 inflammasome activation inhibited TLR-mediated LCN2 secretion. The inhibition of NLRP3 triggers on LCN2 secretion was caused by the inhibited transcription and translation of LCN2. At the same time, no changes in the other cytokines and IκBζ, a well-known transcriptional factor of Lcn2 transcription, were observed. Overall, NLRP3 triggers are a regulator of LCN2 expression suggesting a new linkage of inflammasome activation and LCN2 secretion in the innate immunity.
Keywords:
NLRP3 inflammasome; lipocalin-2; macrophages; nigericin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / immunology
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Adenosine Triphosphate / pharmacology
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Animals
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Female
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Femur / cytology
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Femur / immunology
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Gene Expression Regulation
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Immunity, Innate
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Inflammasomes / drug effects
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Inflammasomes / genetics
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Inflammasomes / immunology*
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Interleukin-1beta / genetics
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Interleukin-1beta / immunology*
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Lipocalin-2 / genetics
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Lipocalin-2 / immunology*
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Lipopolysaccharides / pharmacology
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Macrophages / cytology
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Macrophages / drug effects
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Macrophages / immunology*
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Mice
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Mice, Inbred C57BL
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NLR Family, Pyrin Domain-Containing 3 Protein / genetics
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NLR Family, Pyrin Domain-Containing 3 Protein / immunology*
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Nigericin / pharmacology
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Primary Cell Culture
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RAW 264.7 Cells
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Signal Transduction
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Stem Cells / cytology
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Stem Cells / drug effects
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Stem Cells / immunology
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Tibia / cytology
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Tibia / immunology
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Transcription, Genetic
Substances
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Adaptor Proteins, Signal Transducing
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IL1B protein, mouse
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Inflammasomes
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Interleukin-1beta
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Lipocalin-2
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Lipopolysaccharides
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NLR Family, Pyrin Domain-Containing 3 Protein
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Nfkbiz protein, mouse
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Nlrp3 protein, mouse
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Lcn2 protein, mouse
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Adenosine Triphosphate
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Nigericin