Related Experiment Video

Updated: Aug 21, 2026

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

Non-covalent mTOR inhibition suppresses NLRP3-GSDMD inflammasome-mediated pyroptosis

Xueqin Jiang1, Xinlu Zhang1, Xiaoying Cai1

  • 1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.

Biochemical Pharmacology
|August 20, 2026
PubMed

Insights

Compound CD25 inhibits NLRP3 inflammasome-mediated pyroptosis by targeting mTORC1/2 pathways. This novel inhibitor preserves mitochondrial integrity and reduces inflammatory injury in sepsis and liver injury models, offering a potential therapeutic strategy.

Area of Science:

  • Immunology
  • Cell Biology
  • Pharmacology

Background:

  • Pyroptosis is a key inflammatory cell death pathway regulated by the NLRP3 inflammasome.
  • The mechanistic target of rapamycin (mTOR) pathway influences pyroptosis, but its exact role is unclear.

Purpose of the Study:

  • To investigate the role of mTOR signaling in NLRP3 inflammasome activation.
  • To evaluate compound CD25, a novel mTOR inhibitor, as a modulator of pyroptosis.

Main Methods:

  • Utilized compound CD25, a small-molecule inhibitor targeting mTORC1 and mTORC2.
  • Assessed pyroptosis, inflammasome activation (NLRP3, ASC), gasdermin D (GSDMD) cleavage, and mitochondrial integrity in macrophages.
  • Evaluated CD25 efficacy in murine models of lipopolysaccharide-induced sepsis and acetaminophen-induced acute liver injury.

Main Results:

  • Compound CD25 suppressed NLRP3 inflammasome-mediated pyroptosis.
  • CD25 preserved mitochondrial integrity, inhibited ASC oligomerization, and blocked GSDMD cleavage and pore formation.
  • CD25 administration attenuated inflammatory injury and tissue damage in sepsis and acute liver injury models.

Conclusions:

  • mTOR signaling is a critical regulator of NLRP3 inflammasome-dependent pyroptosis.
  • Compound CD25 demonstrates therapeutic potential for immune-related inflammatory disorders by targeting mTOR signaling.
Keywords:
Acute liver injuryNLRP3 inflammasomeNon-covalent inhibitionPyroptosisSepsismTOR signaling

More Related Videos

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation06:12

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation

Published on: May 3, 2024

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 rapamycin-insensitive companion...
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 heterodimer of NF-κB...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...
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...
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...