Related Experiment Video

Updated: Aug 16, 2025

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
09:04

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

Published on: May 22, 2014

21.0K

Lipoxin A4 attenuates MSU-crystal-induced NLRP3 inflammasome activation through suppressing Nrf2 thereby increasing

You Zhou1,2,3, Yongjun Chen2, Xiaowu Zhong3

  • 1Laboratory Medicine Center, Lanzhou University Second Hospital, Lanzhou, China.

Frontiers in Immunology
|December 26, 2022
PubMed

Insights

Lipoxin A4 (LXA4) reduces gout inflammation by inhibiting NLRP3 inflammasome activation and pyroptosis. This study reveals LXA4

Area of Science:

  • Immunology and Inflammation Research
  • Molecular Mechanisms of Inflammatory Diseases

Background:

  • Gout is a prevalent inflammatory condition.
  • Monosodium urate (MSU) crystal-induced NLRP3 inflammasome activation is central to gout pathogenesis.
  • Lipoxin A4 (LXA4) possesses anti-inflammatory properties, but its effect on MSU-induced NLRP3 inflammasome is unknown.

Purpose of the Study:

  • To investigate the protective effects of LXA4 against MSU-crystal-induced NLRP3 inflammasome activation.
  • To elucidate the underlying molecular mechanisms of LXA4's action in gout inflammation.

Main Methods:

  • Assessed LXA4's impact on NLRP3 inflammasome activation, IL-1β maturation, and pyroptosis in response to MSU crystals.
  • Examined LXA4's effects on oxidative stress markers (ROS, NADPH oxidase, mitochondrial dysfunction) and Nrf2 pathway.
  • Utilized TXNRD2 knockdown and a rat model of gouty arthritis to validate findings.

Main Results:

  • LXA4 inhibited MSU-induced NLRP3 inflammasome assembly, IL-1β maturation, and pyroptosis.
  • LXA4 suppressed oxidative stress by reducing ROS generation and NADPH oxidase activity.
  • LXA4 modulated the Nrf2 pathway, increasing TXNRD2 expression, which was crucial for its anti-inflammatory effects; LXA4 alleviated joint inflammation in a rat model.

Conclusions:

  • LXA4 attenuates MSU-crystal-induced NLRP3 inflammasome activation and gouty arthritis.
  • The mechanism involves suppressing oxidative stress and modulating the Nrf2-TXNRD2 pathway.
  • LXA4 shows potential as a novel therapeutic candidate for gout treatment.
Keywords:
MSUNLRP3 inflammasomeNrf2ROSTXNRD2goutlipoxinA4

More Related Videos

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages06:52

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

Published on: May 21, 2018

10.8K
Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages08:41

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages

Published on: April 6, 2022

2.8K

Related Concept Videos

Formation of Lipopolysaccharides01:19

Formation of Lipopolysaccharides

Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin,...
74
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.5K
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...
6.7K
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