The inflammatory transcriptome of reactive murine astrocytes and implications for their innate immune function

J Neurochem. 2006 Feb;96(3):893-907. doi: 10.1111/j.1471-4159.2005.03622.x. Epub 2006 Jan 9.

Abstract

Upon injury, astrocytes assume an activated state associated with the release of inflammatory mediators. To model this, we stimulated murine primary astrocytes with a complete inflammatory cytokine mix consisting of TNF-alpha, IL-1beta and IFN-gamma. We analysed the transcriptional response of 480 genes at 4 and 16 h after stimulation on a chip designed to give a representative overview over the inflammation-relevant part of the transcriptome of macrophage-like cells. The list of the 182 genes found to be significantly regulated in astrocytes revealed an intriguing co-ordinate regulation of genes linked to the biological processes of antiviral/antimicrobial defence, antigen presentation and facilitation of leucocyte invasion. The latter group was characterized by very high up-regulations of chemokine genes. We also identified regulations of a thymidylate kinase and an interferon-regulated protein with a tetratricopeptide motive, both up to now only known from macrophages. The transcriptional regulations were confirmed on the protein level by a proteomic analysis. These findings taken together suggest that activated astrocytes in brain behave similarly in many respects to inflamed macrophages in the periphery.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / drug effects*
  • Astrocytes / immunology
  • Cell Cycle / genetics
  • Cell Death / genetics
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Cytokines / pharmacology*
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Immunity, Innate / genetics
  • Immunity, Innate / physiology*
  • Immunohistochemistry / methods
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Models, Immunological
  • Nitrites / metabolism
  • Oligonucleotide Array Sequence Analysis / methods
  • Pregnancy
  • Proteomics / methods
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods
  • Stress, Physiological / genetics
  • Time Factors

Substances

  • Chemokine CCL5
  • Cytokines
  • Glial Fibrillary Acidic Protein
  • Nitrites
  • RNA, Messenger