IFN-gamma-mediated transcriptional induction of the IDO (Indolamine 2,3-dioxygenase) gene requires activity of p68/PKR protein kinase

Abstract

We investigated whether the activity of double-stranded RNA activated kinase (p68/PKR) is necessary for induction of IDO (indolamine 2,3 -dioxygenase) gene by IFN-$gamma$. For this purpose, we planned to abrogate the function of cellular wt-PKR gene. Clones of ME180 cells expressing the dominant negative form of PKR were selected in the presence of neomycin. Then these cells were treated with IFN-$gamma$ and accumulation of IDO protein was determined by Western blot analysis. We found that clones expressing the dominant negative form of the PKR gene were not only resistant to IFN-$gamma$-mediated killing, but were also incapable of inducing accumulation of IDO protein after IFN-$gamma$ treatment.