Article Text

PDF
008
GENETICS OF INTERLEUKIN 6 AND SELENOPROTEIN S THAT HAVE A ROLE IN INFLAMMATION AND CORONARY ARTERY DISEASE
  1. H AlHomidani,
  2. K Bodman-Smith,
  3. A Agouni,
  4. FR Green
  1. School of Biosciences and Medicine, University of Surrey, UK

Abstract

Coronary artery disease (CAD) is inflammatory and caused by genetic/environmental factors. Interleukin (IL) 6 is a pro-inflammatory cytokine implicated in CAD. Selenoprotein S (SelS) has recently been implicated in inflammation and endoplasmic reticulum (ER) stress. Several IL-6 and SelS polymorphisms are associated with increased CAD risk and the aim of this project is to investigate in vitro the mechanisms underlying this.

Flow cytometry was used to assess the surface expression of the macrophage differentiation-specific markers CD14 and CD11c, and IL-6r (CD126) by PBMC derived macrophages. mRNA levels were determined by quantitative PCR (QPCR) in lipopolysaccharide (LPS) and IL-1β-stimulated THP-1 cells and in peripheral blood mononuclear cell (PBMC)-derived macrophages from healthy donors.

CD11c-hi, CD14-lo expression on macrophage-like versus monocyte-like PBMCs confirmed their differentiation state. Neither differentiation state nor inflammatory stimulation affected expression of IL-6 or SelS in THP-1 or PBMCs. IL-6 was significantly upregulated in LPS-stimulated THP-1 and PBMC-derived macrophages, consistent with the literature. SelS was upregulated by LPS only in differentiated THP-1 cells. ER stress proteins CHOP (C/EBP homologous protein) and BiP (IgH chain binding protein) were not induced by IL-1β or LPS. CD126 (IL-6r) expression was very low on PBMC-derived macrophages, suggesting that classical IL-6 signalling may not occur in these PBMCs.

In conclusion, this PBMC model of inflammation has been validated, and suggests a lack of classical IL-6 signalling; further analysis by IL-6 and SelS genotype will reveal underlying molecular mechanisms of CAD risk association.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.