Astrogliosis involves activation of retinoic acid-inducible gene-like signaling in the innate immune response after spinal cord injury

Glia. 2012 Mar;60(3):414-21. doi: 10.1002/glia.22275. Epub 2011 Dec 7.


Spinal cord injury (SCI) induces a glial response in which astrocytes become activated and produce inflammatory mediators. The molecular basis for regulation of glial-innate immune responses remains poorly understood. Here, we examined the activation of retinoic acid-inducible gene (RIG)-like receptors (RLRs) and their involvement in regulating inflammation after SCI. We show that astrocytes express two intracellular RLRs: RIG-I and melanoma differentiation-associated gene 5. SCI and stretch injury of cultured astrocytes stimulated RLR signaling as determined by phosphorylation of interferon regulatory factor 3 (IRF3) leading to production of type I interferons (IFNs). RLR signaling stimulation with synthetic ribonucleic acid resulted in RLR activation, phosphorylation of IRF3, and increased expression of glial fibrillary acidic protein (GFAP) and vimentin, two hallmarks of reactive astrocytes. Moreover, mitochondrial E3 ubiquitin protein ligase 1, an RLR inhibitor, decreased production of GFAP and vimentin after RIG-I signaling stimulation. Our findings identify a role for RLR signaling and type I IFN in regulating astrocyte innate immune responses after SCI.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Astrocytes / physiology*
  • Cells, Cultured
  • DEAD-box RNA Helicases / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Female
  • Gene Expression Regulation / drug effects
  • Glial Fibrillary Acidic Protein / metabolism
  • Immunity, Innate / drug effects
  • Immunity, Innate / physiology*
  • Interferon Regulatory Factor-3 / metabolism
  • Interferon Type I / genetics
  • Interferon Type I / metabolism
  • Interferon-Induced Helicase, IFIH1
  • Poly I-C / pharmacology
  • RNA Helicases / metabolism*
  • RNA Helicases / pharmacology
  • RNA, Double-Stranded / pharmacology
  • Rats
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Spinal Cord Injuries / immunology*
  • Spinal Cord Injuries / metabolism*
  • Stress, Mechanical
  • Time Factors
  • Vimentin / metabolism


  • Glial Fibrillary Acidic Protein
  • Interferon Regulatory Factor-3
  • Interferon Type I
  • RNA, Double-Stranded
  • Vimentin
  • RIG-I protein, rat
  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1
  • RNA Helicases
  • Poly I-C