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

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

Research output: Contribution to journalArticle

26 Citations (Scopus)

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
Pages (from-to)414-421
Number of pages8
JournalGLIA
Volume60
Issue number3
DOIs
StatePublished - Mar 1 2012

Fingerprint

Tretinoin
Spinal Cord Injuries
Innate Immunity
Astrocytes
Interferon Regulatory Factor-3
Genes
Glial Fibrillary Acidic Protein
Vimentin
Neuroglia
Interferon alpha-beta Receptor
Phosphorylation
Interferon Type I
Retinoic Acid Receptors
Ubiquitin-Protein Ligases
Melanoma
RNA
Inflammation
Wounds and Injuries

Keywords

  • Astrocytes
  • Innate immunity
  • Neuroinflammation
  • Spinal cord injury

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Astrogliosis involves activation of retinoic acid-inducible gene-like signaling in the innate immune response after spinal cord injury. / de Rivero Vaccari, Juan Pablo P; Minkiewicz, Julia; Wang, Xiaoliang; De Rivero Vaccari, Juan Carlos; German, Ramon; Marcillo, Alexander; Dalton Dietrich, W.; Keane, Robert.

In: GLIA, Vol. 60, No. 3, 01.03.2012, p. 414-421.

Research output: Contribution to journalArticle

de Rivero Vaccari, Juan Pablo P ; Minkiewicz, Julia ; Wang, Xiaoliang ; De Rivero Vaccari, Juan Carlos ; German, Ramon ; Marcillo, Alexander ; Dalton Dietrich, W. ; Keane, Robert. / Astrogliosis involves activation of retinoic acid-inducible gene-like signaling in the innate immune response after spinal cord injury. In: GLIA. 2012 ; Vol. 60, No. 3. pp. 414-421.
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