Related Experiment Video

Updated: Jun 12, 2025

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
06:52

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages

Published on: May 21, 2018

10.7K

mTOR Modulates NLRP3 Inflammasome Activation via Nuclear Translocation and STAT1 Inhibition

Alvaro González-Dominguez1, Shuling Zhang2, Daniel Boy-Ruiz3

  • 1Division of Liver Diseases, Icahn School of Medicine at Mont Sinai, New York, New York, USA.

European Journal of Immunology
|June 11, 2025
PubMed

Insights

Mammalian target of rapamycin (mTOR) regulates NLRP3 inflammasome activation in macrophages. Inhibiting mTOR with rapamycin suppresses inflammasome activity, offering a potential therapeutic strategy for related diseases.

Area of Science:

  • Immunology
  • Cell Biology
  • Metabolic Disease

Background:

  • The NLRP3 inflammasome is a key mediator of inflammatory responses.
  • Dysregulated NLRP3 inflammasome activation is linked to various diseases, including metabolic disorders and neurodegeneration.
  • Its role as a sensor of metabolic danger and stress is increasingly recognized.

Purpose of the Study:

  • To investigate the role of mammalian target of rapamycin (mTOR) in regulating NLRP3 inflammasome activation.
  • To elucidate the mechanism by which mTOR influences NLRP3 inflammasome activity in macrophages.
  • To explore the therapeutic potential of targeting the mTOR-NLRP3 axis.

Main Methods:

  • Utilized cell culture models (macrophages) and mouse models (mTOR knockdown).
  • Assessed NLRP3 inflammasome activation using lipopolysaccharides (LPS) and adenosine triphosphate (ATP) stimulation.
  • Investigated protein-protein interactions, nuclear translocation, and gene/protein expression levels.
  • Employed pharmacological inhibitors including rapamycin and fludarabine.

Main Results:

  • mTOR binds to NLRP3 under basal conditions; this binding decreases upon LPS/ATP stimulation.
  • Rapamycin treatment downregulates mTOR and inhibits NLRP3 inflammasome activation.
  • mTOR knockdown mice showed reduced inflammasome component levels and impaired NLRP3 activation in macrophages.
  • LPS/ATP induced nuclear translocation of mTOR, enhancing NLRP3 activation.
  • mTOR inhibition by rapamycin increased STAT1 phosphorylation, repressing NLRP3; this repression was reversed by fludarabine.

Conclusions:

  • mTOR plays a crucial role in regulating NLRP3 inflammasome activation within the nucleus of macrophages.
  • The mTOR-NLRP3 interaction and subsequent nuclear translocation are key steps in inflammasome activation.
  • Targeting mTOR, potentially in combination with STAT1 modulation, presents a promising therapeutic strategy for controlling NLRP3-mediated inflammation.

More Related Videos

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells09:04

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

20.8K
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

7.4K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.4K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.7K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.3K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K