Expression of IL-27 p28 by Theiler's virus-infected macrophages depends on TLR3 and TLR7 activation of JNK-MAP-kinases

Antiviral Res. 2007 Nov;76(2):159-67. doi: 10.1016/j.antiviral.2007.06.013. Epub 2007 Jul 17.


Theiler's murine encephalomyelitis virus (TMEV) causes a demyelinating disease (DD) due to infection of macrophages, stimulation of macrophage Toll-like receptor (TLR)3 and TLR7 pathways, activation of Mitogen-activated protein kinases (MAPK)s, and production of macrophages cytokines. Because expression of IL-27, a macrophage cytokine composed of p28 and EBI3 subunits, has been implicated in DD, we examined IL-27 subunit mRNA expression during TMEV infection of RAW264.7 cells, a macrophage cell line. TMEV infection of RAW264.7 cells did not affect cell viability, resulted in viral RNA replication, as well as p28 and EBI3 expression. Expression of p28 in TMEV-infected RAW264.7 cells depended on TLR3 and TLR7, as well as JNK but not p38 or ERK MAPKs. Since TMEV causes DD in SJL/J but not B10.S mice we determined the difference in expression of IL-27 subunit mRNA in SJL/J compared to B10.S macrophages. SJL/J macrophages expressed significantly more p28 mRNA after TMEV infection and after stimulation with TLR3 and TLR7 agonists compared with B10.S macrophages. Therefore, macrophages expression of IL-27 p28 mRNA in response to TMEV is due to activation of TLR3, TLR7, and JNK MAPKs pathways.

Publication types

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

MeSH terms

  • Animals
  • Female
  • Gene Expression
  • Interleukins / biosynthesis
  • Interleukins / genetics
  • Interleukins / immunology*
  • JNK Mitogen-Activated Protein Kinases / immunology
  • Macrophages / immunology*
  • Macrophages / virology*
  • Membrane Glycoproteins / immunology*
  • Mice
  • Minor Histocompatibility Antigens
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Cytokine / biosynthesis
  • Receptors, Cytokine / genetics
  • Theilovirus / immunology*
  • Toll-Like Receptor 3 / immunology*
  • Toll-Like Receptor 7 / immunology*


  • Ebi3 protein, mouse
  • Il27 protein, mouse
  • Interleukins
  • Membrane Glycoproteins
  • Minor Histocompatibility Antigens
  • RNA, Messenger
  • Receptors, Cytokine
  • TLR3 protein, mouse
  • Tlr7 protein, mouse
  • Toll-Like Receptor 3
  • Toll-Like Receptor 7
  • JNK Mitogen-Activated Protein Kinases