Fluoride as a factor initiating and potentiating inflammation in THP1 differentiated monocytes/macrophages

Toxicol In Vitro. 2015 Oct;29(7):1661-8. doi: 10.1016/j.tiv.2015.06.024. Epub 2015 Jun 26.

Abstract

It is well known that exposure to fluorides lead to an increased ROS production and enhances the inflammatory reactions. Therefore we decided to examine whether cyclooxygenases (particular COX-2) activity and expression may be changed by fluoride in THP1 macrophages and in this way may change the prostanoids biosynthesis. In the present work we demonstrate that fluoride increased concentration of PGE2 and TXA2 in THP1 macrophages. Following exposure to 1-10 μM NaF, COX-2 protein and COX-2 transcript increased markedly. COX-2 protein up-regulation probably is mediated by ROS, produced during fluoride-induced inflammatory reactions. Additional fluoride activates the transcription factor, nuclear factor (NF)-kappaB, which is involved in the up-regulation of COX-2 gene expression. This study indicated that even in small concentrations fluoride changes the amounts and activity of COX-1 and COX-2 enzymes taking part in the initiating and development of inflammatory process.

Keywords: Cyclooxygenase-2; Fluorine-induced inflammation; Macrophage; Prostaglandin E2; Thromboxane A2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cell Line
  • Cyclooxygenase 1 / genetics
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • Humans
  • Inflammation / metabolism
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Sodium Fluoride / pharmacology*
  • Thromboxane A2 / metabolism

Substances

  • Thromboxane A2
  • Sodium Fluoride
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Dinoprostone