Resolvin D1 down-regulates CYP1A1 and PTGS2 gene in the HUVEC cells treated with benzo(a)pyrene

Pharmacol Rep. 2016 Oct;68(5):939-44. doi: 10.1016/j.pharep.2016.05.005. Epub 2016 Jun 27.

Abstract

Background: Polycyclic aromatic hydrocarbons (PAHs) can interact with lipids and their derivatives and have been known to induce atherosclerosis. The aim of this study was to evaluate the impact of Resolvin D1 (RvD1) on inflammatory-state realted proteins and genes in the human primary umbilical vein endothelial HUVEC cells exposed to benzo(a)pyrene (BaP).

Methods: We analyzed the influence of RvD1 and/or BaP on cyclooxygenase-2 (COX-2), cytosolic prostaglandine E2 synthase (cPGES), glutathione S transferase (GSTM1) and aryl hydrocarbon receptor (AhR) protein expression by Western blot. Additionaly, phospholipase A2 (cPLA2) and cytochrome P450 (CYP1A1) activity, as well as AhR, CYP1A1, phospholipase A2 (PLA2G4A) and prostaglandin synthase 2 (PTGS2) gene expression by qRT-PCR was studied.

Results: RvD1 down-regulates cytochrome P450 (CYP1A1) and prostaglandin synthase 2 (PTGS2) gene expression in HUVEC cells exposed to BaP. Repressesion of COX-2, cPGES and overexpressesion of GSTM1 protein was noted after co-treatment with RvD1 and BaP. After incubation with RvD1 an increase of cPLA2 and a decrease of CYP1A1 activity was observed when compared to BaP treated alone endothelial cells.

Conclusions: Our data suggests that RvD1 can significantly contributes on vascular function and alleviates the harmful effects caused by BaP, which might potentially aid in the repair of the injured endothelium.

Keywords: Benzo(a)pyrene; COX-2; CYP1A1; Environmental stress; HUVEC; Resolvin D1.

MeSH terms

  • Benzo(a)pyrene / pharmacology*
  • Cyclooxygenase 2 / genetics*
  • Cytochrome P-450 CYP1A1 / genetics*
  • Docosahexaenoic Acids / pharmacology*
  • Down-Regulation / drug effects*
  • Gene Expression / drug effects
  • Glutathione Transferase / genetics
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Humans
  • Polycyclic Aromatic Hydrocarbons / metabolism
  • Receptors, Aryl Hydrocarbon / genetics

Substances

  • Polycyclic Aromatic Hydrocarbons
  • Receptors, Aryl Hydrocarbon
  • resolvin D1
  • Docosahexaenoic Acids
  • Benzo(a)pyrene
  • CYP1A1 protein, human
  • Cytochrome P-450 CYP1A1
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Glutathione Transferase
  • glutathione S-transferase M1