Retinoic acid-inducible gene-I mediates RANTES/CCL5 expression in U373MG human astrocytoma cells stimulated with double-stranded RNA

Neurosci Res. 2007 Jun;58(2):199-206. doi: 10.1016/j.neures.2007.02.017. Epub 2007 Mar 3.

Abstract

Retinoic acid-inducible gene-I (RIG-I) mediates part of the cell signaling in response to viral infection. Polyinosinic-polycytidilic acid (poly IC) is a synthetic double-stranded RNA (dsRNA) and mimics viral infection when applied to cell cultures. The CC chemokine, RANTES (regulated on activation, normal T-cell expressed and secreted), is a potent attractant for inflammatory cells such as memory T-lymphocytes, monocytes and eosinophils. In the present study, we demonstrated that poly IC enhances the expression of RIG-I in U373MG human astrocytoma cells. The RNA interference of RIG-I resulted in the suppression of the poly IC-induced RANTES expression. Pretreatment of the cells with SB203580, an inhibitor of p38 mitogen-activated protein kinase, and dexamethasone inhibited the poly IC-induced expression of RIG-I. Furthermore, poly IC upregulated RIG-I in normal human astrocytes in culture and the in vivo injection of poly IC into the striatum of the mouse brain induced the expression of RIG-I in astrocytes. We conclude that RIG-I may be involved in immune reactions against viral infection, at least in part, through the regulation of RANTES expression in astrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytoma / metabolism*
  • Cell Line, Tumor
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Imidazoles / pharmacology
  • Interferon Inducers / pharmacology
  • Poly I-C / pharmacology
  • Pyridines / pharmacology
  • RNA, Double-Stranded / pharmacology*
  • Time Factors
  • Trans-Activators
  • Transcription Factors / metabolism*

Substances

  • Chemokine CCL5
  • Enzyme Inhibitors
  • Glial Fibrillary Acidic Protein
  • Imidazoles
  • Interferon Inducers
  • Pyridines
  • RAI1 protein, human
  • RNA, Double-Stranded
  • Trans-Activators
  • Transcription Factors
  • Poly I-C
  • SB 203580