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Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
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The protective effect of quercetin on macrophage pyroptosis via TLR2/Myd88/NF-κB and ROS/AMPK pathway

Xing Luo1, Xiaoyi Bao1, Xiuzhu Weng2

  • 1Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China; Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin 150001, PR China.

Life Sciences
|October 24, 2021
PubMed
Abstract

Insights

Quercetin, a natural flavonoid, protects macrophages from pyroptosis by inhibiting NLRP3 inflammasome activation. It reduces inflammatory markers and cell death through the TLR2/Myd88/NF-κB and ROS/AMPK pathways.

Area of Science:

  • Immunology
  • Cell Biology
  • Pharmacology

Background:

  • Pyroptosis is a key inflammatory cell death pathway implicated in various diseases.
  • Quercetin, a flavonoid, exhibits anti-inflammatory properties, but its impact on macrophage pyroptosis remains unexplored.

Purpose of the Study:

  • To investigate the effects of quercetin on macrophage pyroptosis.
  • To elucidate the underlying molecular mechanisms of quercetin's action.

Main Methods:

  • THP-1 macrophages were subjected to lipopolysaccharide/adenosine triphosphate (LPS/ATP) to induce pyroptosis.
  • Cell viability, morphology, membrane integrity, and inflammasome component expression (NLRP3, caspase-1, IL-1β, GSDMD) were assessed.
  • Reactive oxygen species (ROS) levels, P65 nuclear translocation, and signaling pathways (TLR2/Myd88, AMPK) were analyzed.

Main Results:

  • Quercetin significantly reduced pyroptosis markers, including NLRP3, cleaved-caspase-1, IL-1β, and N-GSDMD, in a dose-dependent manner.
  • Quercetin inhibited NLRP3 inflammasome activation by suppressing ROS overproduction and NF-κB (P65) nuclear translocation.
  • Quercetin downregulated TLR2/Myd88 and phosphorylated AMPK (p-AMPK) signaling, which were implicated in pyroptosis.

Conclusions:

  • Quercetin demonstrates a protective effect against macrophage pyroptosis.
  • The mechanism involves the modulation of the TLR2/Myd88/NF-κB and ROS/AMPK signaling pathways.
Keywords:
MacrophageNF-κB pathwayNLRP3 inflammasomePyroptosisQuercetinROS

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