Differential expression of miRNA-146a-regulated inflammatory genes in human primary neural, astroglial and microglial cells

Neurosci Lett. 2011 Jul 20;499(2):109-13. doi: 10.1016/j.neulet.2011.05.044. Epub 2011 May 26.


MicroRNA-146a (miRNA-146a) is an inducible, 22 nucleotide, small RNA over-expressed in Alzheimer's disease (AD) brain. Up-regulated miRNA-146a targets several inflammation-related and membrane-associated messenger RNAs (mRNAs), including those encoding complement factor-H (CFH) and the interleukin-1 receptor associated kinase-1 (IRAK-1), resulting in significant decreases in their expression (p<0.05, ANOVA). In this study we assayed miRNA-146a, CFH, IRAK-1 and tetraspanin-12 (TSPAN12), abundances in primary human neuronal-glial (HNG) co-cultures, in human astroglial (HAG) and microglial (HMG) cells stressed with Aβ42 peptide and tumor necrosis factor alpha (TNFα). The results indicate a consistent inverse relationship between miRNA-146a and CFH, IRAK-1 and TSPAN12 expression levels, and indicate that HNG, HAG and HMG cell types each respond differently to Aβ42-peptide+TNFα-triggered stress. While the strongest miRNA-146a-IRAK-1 response was found in HAG cells, the largest miRNA-146a-TSPAN12 response was found in HNG cells, and the most significant miRNA-146a-CFH changes were found in HMG cells, the 'resident scavenging macrophages' of the brain.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / physiology
  • Astrocytes / pathology
  • Astrocytes / physiology*
  • Cells, Cultured
  • Coculture Techniques
  • Complement Factor H / antagonists & inhibitors
  • Complement Factor H / genetics
  • Gene Expression Regulation*
  • Humans
  • Inflammation Mediators / physiology*
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • MicroRNAs / physiology
  • Microglia / pathology
  • Microglia / physiology*
  • Neurons / pathology
  • Neurons / physiology*
  • Peptide Fragments / physiology
  • Tumor Necrosis Factor-alpha / physiology


  • Amyloid beta-Peptides
  • Inflammation Mediators
  • MIRN146 microRNA, human
  • MicroRNAs
  • Peptide Fragments
  • Tumor Necrosis Factor-alpha
  • amyloid beta-protein (1-42)
  • Complement Factor H