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

Juan Pablo de Rivero Vaccari, Julia Minkiewicz, Xiaoliang Wang, Juan Carlos De Rivero Vaccari, Ramon German, Alex E. Marcillo, W. Dalton Dietrich, Robert W. Keane

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)414-421
Number of pages8
JournalGlia
Volume60
Issue number3
DOIs
StatePublished - Mar 2012

Keywords

  • Astrocytes
  • Innate immunity
  • Neuroinflammation
  • Spinal cord injury

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

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