ERK-MAP-kinases differentially regulate expression of IL-23 p19 compared with p40 and IFN-β in Theiler's virus-infected RAW264.7 cells

Theiler's murine encephalomyelitis virus (TMEV) infection of macrophages induces a demyelinating disease (DD) in certain strains of mice that is similar to human multiple sclerosis. In contrast to IFN-β, expression of IL-23 p19 and p40 subunits by macrophages in response to TMEV may contribute to DD. TMEV infection of macrophages likely induces IL-23 and IFN-β by activating p38 or ERK MAP-kinases (MAPK) and the p38 substrate ATF-2 within 30 min. To determine the role of MAPKs in TMEV-induced IL-23 and IFN-β expression, RAW264.7 cells were pretreated with SB203580 or U0126, inhibitors of p38 and ERK MAPKs, respectively. SB203580 significantly increased TMEV-induced p19 but decreased p40 expression. In contrast, U0126 decreased p19 and increased TMEV-induced p40 and IFN-β expression. Interestingly, U0126 prolonged TMEV-induced ATF-2 activation to at least 3 h. Thus ERK MAPKs regulate expression of TMEV-induced p19 differently than p40 and IFN-β suggesting the benefits of U0126 in treatment of DD.