ERK-MAP-kinases differentially regulate expression of IL-23 p19 compared with p40 and IFN-beta 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-beta, 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-beta 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-beta 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-beta expression. Interestingly, U0126 prolonged TMEV-induced ATF-2 activation to at least 3h. Thus ERK MAPKs regulate expression of TMEV-induced p19 differently than p40 and IFN-beta suggesting the benefits of U0126 in treatment of DD.
Petro
Thomas M
TM
Department of Oral Biology, the Nebraska Center for Virology, University of Nebraska Medical Center, Lincoln, NE 68583, USA. tpetro@unmc.edu
D051698:Activating Transcription Factor 2; D000818:Animals; D018188:Cardiovirus Infections / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics* / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism; D017945:Theilovirus / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; C508840:IL23A protein, human; C508841:Il23a protein, mouse; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D021122:Protein Subunits; D014157:Transcription Factors; D018664:Interleukin-12; D016899:Interferon-beta; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases