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Inflammasome Activation and IL-1β Release Triggered by Nanosecond Pulsed Electric Fields in Murine Innate Immune Cells and Skin

J Immunol · 2024 · Harm · Low evidence

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HarmLow evidencePaper 6746

200-ns pulsed electric fields induced ASC aggregation, caspase-1 activation, and IL-1β release in multiple murine innate immune cell types and in vivo in mouse skin. Potassium efflux was partially responsible for inflammasome activation, and experiments with …

Study snapshot

PublicationJ Immunol · 2024
Study typeanimal
Reported directionHarm
Evidence ratingLow

Abstract

Although electric field-induced cell membrane permeabilization (electroporation) is used in a wide range of clinical applications from cancer therapy to cardiac ablation, the cellular- and molecular-level details of the processes that determine the success or failure of these treatments are poorly understood. Nanosecond pulsed electric field (nsPEF)-based tumor therapies are known to have an immune component, but whether and how immune cells sense the electroporative damage and respond to it have not been demonstrated. Damage- and pathogen-associated stresses drive inflammation via activation of cytosolic multiprotein platforms known as inflammasomes. The assembly of inflammasome complexes triggers caspase-1-dependent secretion of IL-1β and in many settings a form of cell death called pyroptosis. In this study we tested the hypothesis that the nsPEF damage is sensed intracellularly by the NLRP3 inflammasome. We found that 200-ns PEFs induced aggregation of the inflammasome adaptor protein ASC, activation of caspase-1, and triggered IL-1β release in multiple innate immune cell types (J774A.1 macrophages, bone marrow-derived macrophages, and dendritic cells) and in vivo in mouse skin. Efflux of potassium from the permeabilized cell plasma membrane was partially responsible for nsPEF-induced inflammasome activation. Based on results from experiments using both the NRLP3-specific inhibitor MCC950 and NLRP3 knockout cells, we propose that the damage created by nsPEFs generates a set of stimuli for the inflammasome and that more than one sensor can drive IL-1β release in response to electrical pulse stimulation. This study shows, to our knowledge, for the first time, that PEFs activate the inflammasome, suggesting that this pathway alarms the immune system after treatment.

Machine Enhanced Logic

AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typeanimal
Effect directionharm
PopulationMurine innate immune cells (J774A.1 macrophages, bone marrow-derived macrophages, dendritic cells) and mouse skin (in vivo)
Sample sizeNot supplied
Exposure200-ns pulses
Evidence strengthLowConfidence: 74% · Peer reviewed: yes

Main findings

200-ns pulsed electric fields induced ASC aggregation, caspase-1 activation, and IL-1β release in multiple murine innate immune cell types and in vivo in mouse skin. Potassium efflux was partially responsible for inflammasome activation, and experiments with MCC950 and NLRP3 knockout cells suggested NLRP3 contributes but that more than one sensor may drive IL-1β release in response to electrical pulse stimulation.

Outcomes measured

  • ASC aggregation (inflammasome adaptor protein)
  • caspase-1 activation
  • IL-1β release/secretion
  • NLRP3 inflammasome involvement (inhibitor MCC950; NLRP3 knockout)
  • potassium efflux contribution
  • pyroptosis (described as associated outcome in context)

Limitations

  • Sample size not reported in provided abstract/metadata
  • Exposure parameters beyond pulse duration (e.g., field strength, number of pulses) not provided in abstract
  • Mechanistic inference about multiple sensors is described as a proposal; specific alternative sensors not identified in abstract
View raw extracted JSON
{
  "study_type": "animal",
  "exposure": {
    "band": null,
    "source": "nanosecond pulsed electric fields (electroporation)",
    "frequency_mhz": null,
    "sar_wkg": null,
    "duration": "200-ns pulses"
  },
  "population": "Murine innate immune cells (J774A.1 macrophages, bone marrow-derived macrophages, dendritic cells) and mouse skin (in vivo)",
  "sample_size": null,
  "outcomes": [
    "ASC aggregation (inflammasome adaptor protein)",
    "caspase-1 activation",
    "IL-1β release/secretion",
    "NLRP3 inflammasome involvement (inhibitor MCC950; NLRP3 knockout)",
    "potassium efflux contribution",
    "pyroptosis (described as associated outcome in context)"
  ],
  "main_findings": "200-ns pulsed electric fields induced ASC aggregation, caspase-1 activation, and IL-1β release in multiple murine innate immune cell types and in vivo in mouse skin. Potassium efflux was partially responsible for inflammasome activation, and experiments with MCC950 and NLRP3 knockout cells suggested NLRP3 contributes but that more than one sensor may drive IL-1β release in response to electrical pulse stimulation.",
  "effect_direction": "harm",
  "limitations": [
    "Sample size not reported in provided abstract/metadata",
    "Exposure parameters beyond pulse duration (e.g., field strength, number of pulses) not provided in abstract",
    "Mechanistic inference about multiple sensors is described as a proposal; specific alternative sensors not identified in abstract"
  ],
  "evidence_strength": "low",
  "confidence": 0.74,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "nanosecond pulsed electric fields",
    "nsPEF",
    "electroporation",
    "inflammasome",
    "NLRP3",
    "ASC",
    "caspase-1",
    "IL-1β",
    "macrophages",
    "dendritic cells",
    "mouse skin",
    "potassium efflux",
    "MCC950"
  ],
  "suggested_hubs": [
    {
      "slug": "other",
      "weight": 0.35,
      "reason": "Study concerns pulsed electric fields/electroporation and immune inflammasome activation rather than common environmental RF/ELF exposure sources."
    }
  ]
}
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AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.4049/jimmunol.2200881
PubMed: 38047899

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