Diclofenac inhibits 27-hydroxycholesterol-induced inflammation

Biochem Biophys Res Commun. 2016 Sep 23;478(3):1456-61. doi: 10.1016/j.bbrc.2016.08.145. Epub 2016 Aug 26.

Abstract

27-Hydroxycholesterol (27OHChol) is a cholesterol oxidation product that induces inflammation. In the current study we investigated the effects of diclofenac on inflammatory responses caused by 27OHChol using human monocyte/macrophage (THP-1) cells. Transcription and secretion of CCL2, CCL3, and CCL4 chemokines enhanced by 27OHChol were significantly attenuated by diclofenac in a concentration dependent manner. Migrations of monocytic cells and CCR5-positive Jurkat T cells were reduced proportionally to the concentrations of diclofenac. Superproduction of CCL2 and monocytic cell migration induced by 27OHChol plus LPS were significantly attenuated by diclofenac. Diclofenac also attenuated transcription of MMP-9 and release of its active gene product. These results indicate that diclofenac inhibits 27OHChol-induced inflammatory responses, thereby suppressing inflammation in a milieu rich in cholesterol oxidation products.

Keywords: 27-Hydroxycholesterol; Diclofenac; Inflammation; Macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Movement / drug effects
  • Chemokine CCL2
  • Diclofenac / pharmacology*
  • Humans
  • Hydroxycholesterols / toxicity*
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Ligands
  • Matrix Metalloproteinase 9 / metabolism
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Receptors, CCR5 / metabolism
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism

Substances

  • Chemokine CCL2
  • Hydroxycholesterols
  • Ligands
  • Receptors, CCR5
  • Diclofenac
  • 27-hydroxycholesterol
  • Matrix Metalloproteinase 9