Stimulation-specific contribution of p38 and JNK to IFN-beta gene expression in human macrophages.
Induction of interferon-beta (IFN-beta) gene expression is a tightly regulated process, and a plethora of studies identified the signal transduction pathway TANK-binding kinase-1 (TBK-1)/IFN regulatory factor-3 (IRF-3) as essential to the induction of IFN-beta gene expression. Data regarding the role of p38 and JNK are rare, however. We investigated the contribution of these kinases to IFN-beta expression in human macrophages treated with poly(I:C), lipopolysaccharide (LPS), Sendai virus, or vesicular stomatitis virus (VSV). We found that all the stimuli induced IFN-beta mRNA, albeit to a different extent. Whereas LPS and VSV induced the phosphorylation of p38 and JNK, neither poly(I:C) nor Sendai virus led to the detection of phosphospecific signals. When inhibiting p38, a VSV-triggered IFN-beta mRNA response was inhibited, whereas inhibiting JNK suppressed an LPS-triggered response, but only when macrophages were primed with IFN-gamma. Neither poly(I:C)-induced nor Sendai virus-induced IFN-beta mRNA expression was affected when p38 and JNK were inhibited. Collectively, the data show that the contribution of p38 and JNK to the expression of IFN-beta occurs in a stimulation-specific manner in human macrophages.
Reimer
Thornik
T
Institute of Veterinary Virology, University of Bern, CH-3001 Bern, Switzerland. reimer@ivv.unibe.ch
Schweizer
Matthias
M
Jungi
Thomas W
TW
D015870:Gene Expression; D006801:Humans; D007369:Interferon Inducers; D016899:Interferon-beta / Q000235:genetics*; D007371:Interferon-gamma / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D011070:Poly I-C / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D029082:Sendai virus / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D007369:Interferon Inducers; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016899:Interferon-beta; D007371:Interferon-gamma; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D011070:Poly I-C