Defective binding of IRFs to the initiator element of interleukin‐1β‐converting enzyme (ICE) promoter in an interferon‐resistant Daudi subline

Abstract
To investigate mechanisms of interferon (IFN) resistance, we have established an IFN-resistant Daudi subline (Daudires), which is 1×104 times more resistant to IFN-α than parental cells. Among the IFN-inducible genes examined, only ICE mRNA expression was deficient in Daudires cells. We then analyzed the regulatory mechanisms of ICE transcription, and found that IFN-induced activation of the ICE promoter was dependent on the binding of IRFs to its initiator (Inr) element. Inr binding of IRFs was markedly diminished in Daudires cells, and forced expression of IRF-1 was able to activate the ICE promoter to the level of parental cells. These results suggest that IRFs and their target genes, as represented by ICE in this study, are involved in IFN resistance.