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.
Hause
Lara
L
Department of Oral Biology and the Nebraska Center for Virology, University of Nebraska Medical Center, Lincoln, NE 68583, USA.
Al-Salleeh
Fahd M
FM
Petro
Thomas M
TM
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