C/T conversion alters interleukin-1A promoter function in a human astrocyte cell line

Life Sci. 2007 Feb 27;80(12):1152-6. doi: 10.1016/j.lfs.2006.12.011. Epub 2006 Dec 23.

Abstract

Recently, association of an interleukin-1A promoter polymorphism (-889, thymine/thymine (T/T)) with Alzheimer's disease was reported, suggesting that this cytokine may play an important role in disease development. To understand the mechanism underlying the interleukin-1A promoter's role in Alzheimer's disease, a study comparing promoter function of an interleukin-1A polymorphism was performed in the SVG astroglia cell line. The effects of thymine and cytosine on transcriptional activity of the interleukin-1A promoter were analyzed by testing luciferase-reporter activity in transfected SVG cells. Our results demonstrate that cytosine/thymine conversion increases activity of the interleukin-1A promoter in SVG cells. Both sodium salicylate and lovastatin are able to block induced promoter activities in astroglial cells. Induced promoter activity by the polymorphism (T/T) may result in the upregulation of interleukin-1alpha protein and "cytokine cycle" amplification, which may promote disease development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / genetics*
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Cell Line
  • Cytosine
  • Humans
  • Interleukin-1alpha / genetics*
  • Lovastatin / pharmacology
  • Luciferases / genetics
  • Plasmids
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / genetics*
  • Salicylates / pharmacology
  • Thymine
  • Transfection

Substances

  • IL1A protein, human
  • Interleukin-1alpha
  • Salicylates
  • Cytosine
  • Lovastatin
  • Luciferases
  • Thymine