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Updated: Dec 18, 2025

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

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Induction of ASC pyroptosis requires gasdermin D or caspase-1/11-dependent mediators and IFNβ from pyroptotic

Cuiping Zhang1,2, Caiqi Zhao3,4, Xiaoyan Chen1

  • 1Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, 200032, Shanghai, China.

Cell Death & Disease
|June 20, 2020
PubMed

Insights

Mesenchymal stem cells (MSCs) do not undergo pyroptosis directly but can be induced by inflammatory mediators from dying immune cells. This process requires specific macrophage-derived factors and interferon-beta, impacting bacterial clearance.

Area of Science:

  • Immunology
  • Cell Biology
  • Regenerative Medicine

Background:

  • Mesenchymal stem cells (MSCs) are vital in cell-based therapies.
  • Inflammatory conditions can compromise MSC survival and efficacy.
  • Pyroptosis, a form of programmed cell death, is crucial in immune responses, but its role in MSCs is unknown.

Purpose of the Study:

  • To investigate whether adipose-tissue-derived mesenchymal stem cells (ASCs) undergo pyroptosis.
  • To elucidate the mechanisms and biological significance of ASC pyroptosis.
  • To determine the role of inflammatory mediators in ASC pyroptosis.

Main Methods:

  • ASCs were exposed to various inflammatory stimuli and conditioned media from pyroptotic bone marrow-derived macrophages (BMDMs).
  • Genetic manipulation (Gsdmd/Caspase-1/11 knockout) in BMDMs and inhibition of caspases in ASCs were employed.
  • RNA sequencing (RNA-seq) was performed on pyroptotic ASCs.
  • Bactericidal assays were conducted using pyroptotic ASCs against P. Aeruginosa.

Main Results:

  • ASCs did not undergo pyroptosis upon direct stimulation with LPS, flagellin, dsDNA, or nigericin.
  • Culture media from pyroptotic BMDMs induced pyroptosis in ASCs, dependent on Gasdermin D and Caspase-1/11 in BMDMs.
  • IFN-stimulated genes were upregulated in pyroptotic ASCs, and exogenous IFNβ enhanced the process.
  • Pyroptotic ASCs exhibited reduced ability to kill P. Aeruginosa.

Conclusions:

  • ASC pyroptosis is triggered indirectly by mediators released from pyroptotic macrophages.
  • Gasdermin D and Caspase-1/11 in macrophages, along with IFNβ, are critical for inducing ASC pyroptosis.
  • Pyroptosis impairs the antibacterial function of ASCs, suggesting implications for their therapeutic use.

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