Expression of IL-27 p28 by Theiler's virus-infected macrophages depends on TLR3 and TLR7 activation of JNK-MAP-kinases.
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.
Department of Oral Biology and the Nebraska Center for Virology, University of Nebraska Medical Center, Lincoln, NE 68583, USA.
Lara
L
Hause
Fahd M
FM
Al-Salleeh
Thomas M
TM
Petro
D000818:Animals; D005260:Female; D015870:Gene Expression; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000821:virology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D015778:Minor Histocompatibility Antigens; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D017945:Theilovirus / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology*
C499601:Ebi3 protein, mouse; C486767:Il27 protein, mouse; D007378:Interleukins; D008562:Membrane Glycoproteins; D015778:Minor Histocompatibility Antigens; D012333:RNA, Messenger; D018121:Receptors, Cytokine; C519703:TLR3 protein, mouse; C477038:Tlr7 protein, mouse; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D048031:JNK Mitogen-Activated Protein Kinases