The role and mechanism of NLRP3 in wasp venom-induced acute kidney injury

Toxicon. 2024 Feb 1:238:107570. doi: 10.1016/j.toxicon.2023.107570. Epub 2023 Dec 15.

Abstract

Background: Inflammation and pyroptosis have crucial impacts on the development of acute kidney injury (AKI) and have been validated in a variety of existing AKI animal models. However, the mechanisms underlying wasp venom-induced AKI are still unclear. The involvement of nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) in some mouse models of AKI has been extensively documented, and its crucial function in controlling inflammation and pyroptosis has been highlighted. The objective of our study was to investigate the role and mechanism of NLRP3 in inflammation and pyroptosis associated with wasp venom-induced AKI.

Methods: A mouse model of AKI induced by wasp venom pre-injected with an NLRP3 inhibitor was used to study the role and mechanism of NLRP3. To verify the importance of NLRP3, western blotting was performed to assess the expression of NLRP3, caspase-1 p20, and gasdermin D (GSDMD)-N. Additionally, quantitative real-time polymerase was used to determine the expression of NLRP3, caspase-1, and GSDMD. Furthermore, enzyme-linked immunosorbent assay was utilized to measure the levels of interleukin (IL)-1β and IL-18.

Results: NLRP3 was found to be the downstream signal of the stimulator of interferon genes in the wasp sting venom-induced AKI model. The administration of wasp venom in mice significantly upregulated the expression of NLRP3, leading to renal dysfunction, inflammation, and pyroptosis. Treatment with an NLRP3 inhibitor reversed the renal damage induced by wasp venom and attenuated pathological injury, inflammatory response, and pyroptosis.

Conclusion: NLRP3 activation is associated with renal failure, inflammatory response and pyroptosis in the hyper early phase of wasp venom-induced AKI. The inhibition of NLRP3 significantly weakened this phenomenon. These findings could potentially offer a viable therapeutic approach for AKI triggered by wasp venom.

Keywords: Acute kidney injury; Inflammation; Nucleotide-binding oligomerization domain-like receptor protein 3; Pyroptosis; Wasp venom.

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Animals
  • Caspase 1
  • Caspases
  • Disease Models, Animal
  • Inflammation / chemically induced
  • Insect Bites and Stings*
  • Interleukin-1beta
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Wasp Venoms* / toxicity

Substances

  • Caspase 1
  • Caspases
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Wasp Venoms