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Ochratoxin A induces NLRP3 inflammasome-mediated pyroptosis via activation of ROS modulated by autophagy in vitro

Kai Liu1, Dongmei Yue1, Xinru Mao1

  • 1College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China; Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.

Ecotoxicology and Environmental Safety
|July 30, 2026
PubMed

Insights

Ochratoxin A (OTA) causes kidney damage by triggering pyroptosis via the ROS/NLRP3 inflammasome pathway. Autophagy negatively regulates this process, offering a potential therapeutic target for OTA-induced nephrotoxicity.

Area of Science:

  • Toxicology
  • Cell Biology
  • Immunology

Background:

  • Ochratoxin A (OTA) is a prevalent food contaminant linked to kidney fibrosis via pyroptosis.
  • The precise mechanisms of OTA nephrotoxicity and the role of autophagy remain unclear.

Purpose of the Study:

  • To investigate the role of the autophagic-inflammasomal pathway in OTA-induced pyroptosis in vitro.
  • To elucidate the involvement of reactive oxygen species (ROS) and the NLRP3 inflammasome in OTA nephrotoxicity.

Main Methods:

  • Cell viability assays (IC50 determination) in PK-15 cells.
  • Quantitative PCR, Western blotting, and immunofluorescence staining to assess cytokine expression, pyroptosis, and inflammasome formation.
  • Inhibitor treatments (MCC950, 3-MA) and gene knockdown (caspase-1, ATG5) to probe pathway involvement.

Main Results:

  • OTA (5.9 µM IC50) dose-dependently reduced cell viability and increased pro-inflammatory cytokines (TNF-α, IL-1β, IL-18, IL-6).
  • OTA induced pyroptosis and NLRP3 inflammasome formation, which were reversed by MCC950 or caspase-1 knockdown.
  • ROS generation was critical for OTA-induced NLRP3 inflammasome activation and pyroptosis.
  • OTA induced autophagy via the AKT/mTOR pathway; autophagy inhibition exacerbated ROS and NLRP3 inflammasome activation.

Conclusions:

  • ROS/NLRP3 inflammasome-mediated pyroptosis is implicated in low-level OTA-induced nephrotoxicity.
  • Autophagy negatively regulates this pathway, suggesting it as a potential therapeutic target for OTA toxicity.
Keywords:
AutophagyNLRP3 inflammasomeOchratoxin APyroptosisReactive Oxidative stress

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