Potential requirement of a functional double-stranded RNA-dependent protein kinase (PKR) for the tumoricidal activation of macrophages by lipopolysaccharide or IFN-αβ, but not IFN-γ

G. L. Gusella, T. Musso, S. E. Rottschafer, K. Pulkki, L. Varesio

Research output: Contribution to journalArticlepeer-review

Abstract

We analyzed the expression of the dsRNA-dependent protein kinase (PKR) during the activation of murine macrophages to the tumoricidal state by LPS and/or IFNs. LPS induced PKR expression in a dose-dependent manner at levels that were comparable with those observed in response to IFNs. By using the PKR inhibitor 2-aminopurine (2-AP), we have shown that the pathways of macrophage tumoricidal activation elicited by LPS and IFN-αβ, but not by IFN-γ, included a 2-AP-sensitive step. In fact, LPS- and IFN-αβ-induced activation was inhibited by 2-AP, whereas the activation by IFN-γ was not affected by the presence of the inhibitor. 2-AP did not affect the activation of protein kinase C or protein kinase A in intact cells. In the presence of 2-AP the up-regulation of IFN-β mRNA by LPS was specifically inhibited, whereas the expression of glyceraldehyde-3-phosphate dehydrogenase mRNA or the induction of PKR remained unchanged, thereby demonstrating that 2-AP inhibited selective macrophage genes. The differential sensitivity to 2-AP suggested that the expression of a functional PKR may be required for the macrophage tumoricidal response triggered by LPS and IFN-αβ but not IFN- γ.

Original languageEnglish
Pages (from-to)345-354
Number of pages10
JournalJournal of Immunology
Volume154
Issue number1
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Immunology

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