IL-17A activates ERK1/2 and enhances differentiation of oligodendrocyte progenitor cells

Glia. 2015 May;63(5):768-79. doi: 10.1002/glia.22783. Epub 2014 Dec 31.

Abstract

Inflammatory signals present in demyelinated multiple sclerosis lesions affect the reparative remyelination process conducted by oligodendrocyte progenitor cells (OPCs). Interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 have differing effects on the viability and growth of OPCs, however the effects of IL-17A are largely unknown. Primary murine OPCs were stimulated with IL-17A and their viability, proliferation, and maturation were assessed in culture. IL-17A-stimulated OPCs exited the cell cycle and differentiated with no loss in viability. Expression of the myelin-specific protein, proteolipid protein, increased in a cerebellar slice culture assay in the presence of IL-17A. Downstream, IL-17A activated ERK1/2 within 15 min and induced chemokine expression in 2 days. These results demonstrate that IL-17A exposure stimulates OPCs to mature and participate in the inflammatory response.

Keywords: ERK; chemokine; inflammation; interleukin-17; myelin; oligodendrocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Flow Cytometry
  • Freund's Adjuvant / toxicity
  • Gene Expression Regulation / drug effects
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • In Vitro Techniques
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myelin Proteolipid Protein / genetics
  • Myelin-Oligodendrocyte Glycoprotein / toxicity
  • Oligodendroglia / drug effects*
  • Oligodendroglia / enzymology*
  • Organ Culture Techniques
  • Peptide Fragments / toxicity
  • Receptors, Interleukin-17 / deficiency
  • Receptors, Interleukin-17 / genetics
  • Stem Cells / drug effects*
  • Stem Cells / physiology

Substances

  • Cytokines
  • Il17ra protein, mouse
  • Myelin Proteolipid Protein
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Plp1 protein, mouse
  • Receptors, Interleukin-17
  • myelin oligodendrocyte glycoprotein (35-55)
  • Green Fluorescent Proteins
  • Freund's Adjuvant