Plasticizer DBP Activates NLRP3 Inflammasome through the P2X7 Receptor in HepG2 and L02 Cells

J Biochem Mol Toxicol. 2016 Apr;30(4):178-85. doi: 10.1002/jbt.21776. Epub 2015 Nov 20.

Abstract

Ditubyl phthalate (DBP), one of the most widely used plasticizers, can migrate out to contaminate our bodies and environment. A number of studies have showed that DBP is closely related to liver pathological changes and diseases. Inflammasomes are multiprotein complexes composed of procaspase and pattern recognition receptors such as Nucleotide oligomerization domain (NOD) like receptor family, pyrin domain containing 3 (NLRP3). Activation of NLRP3 inflammasome is implicated in the pathogeneses of liver damage. The aim of this study was to determine the effects of DBP on NLRP3 inflammasome. We found that DBP triggered the activation of NLRP3 inflammasome in hepatocyte cell lines. By using Ca-074-Me, N-acetylcysteine and KN-62, we observed that the P2X7 receptor participated in the DBP-induced activation of NLRP3 inflammasome. DBP could also trigger the ATP release. In conclusion, we demonstrated that DBP is one of the activator of NLRP3 inflammasome and may play an important role in liver damage.

Keywords: DBP; NLRP3 Inflammasome; P2X7 Receptor; Plasticizer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Dibutyl Phthalate / toxicity*
  • Hep G2 Cells
  • Humans
  • Inflammasomes / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Plasticizers / toxicity*
  • Receptors, Purinergic P2X7 / metabolism*

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Plasticizers
  • Receptors, Purinergic P2X7
  • Dibutyl Phthalate
  • Adenosine Triphosphate