PM2.5 exposure promotes the progression of acute kidney injury by activating NLRP3-mediated macrophage inflammatory response

Ecotoxicol Environ Saf. 2024 Jun 15:278:116454. doi: 10.1016/j.ecoenv.2024.116454. Epub 2024 May 14.

Abstract

Aim: We reveal the mechanism of action whereby ambient PM2.5 promotes kidney injury.

Methods: Using C57BL/6 mice, the effects of PM2.5 exposure on the acute kidney injury (AKI) were investigated, including renal function changes, expression of inflammatory cytokines, histopathological changes, as well as activation of nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3（NLRP3）. The effects of PM2.5 on renal injury after NLRP3 inhibition were explored using NLRP3 inhibitor (MCC950) and NLRP3 knockout mice. The effects of PM2.5 on the inflammatory response of renal macrophages were investigated at the cellular level.

Results: PM2.5 exposure could promote kidney injury, NLRP3 activation and inflammatory response in mice. After using MCC950 and NLRP3 knockout mice, the effects of PM2.5 and the kidney injury could be inhibited. The cellular-level results also suggested that MCC950 could inhibit the effects of PM2.5.

Conclusion: PM2.5 can promote the progression of AKI and aggravate tissue inflammation through NLRP3, which is an important environmental toxicological mechanism of PM2.5.

Keywords: PM(2.5) ；kidney injury；NLRP3；inflammatory response.

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / pathology
  • Air Pollutants / toxicity
  • Animals
  • Furans / toxicity
  • Indenes / toxicity
  • Inflammation* / chemically induced
  • Macrophages* / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Mice, Knockout*
  • NLR Family, Pyrin Domain-Containing 3 Protein* / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Particulate Matter* / toxicity
  • Sulfonamides / pharmacology
  • Sulfonamides / toxicity
  • Sulfones / toxicity

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Particulate Matter
  • Nlrp3 protein, mouse
  • N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide
  • Sulfonamides
  • Indenes
  • Air Pollutants
  • Furans
  • Sulfones