Journal
EMBO JOURNAL
Volume 19, Issue 14, Pages 3630-3638Publisher
WILEY-BLACKWELL
DOI: 10.1093/emboj/19.14.3630
Keywords
dsRNA; IFN-gamma; macrophage; PKR
Categories
Funding
- NIAID NIH HHS [AI42394, AI44458, R01 AI044458] Funding Source: Medline
- NIDDK NIH HHS [R01 DK052194, DK52194] Funding Source: Medline
Ask authors/readers for more resources
In this study, the role of the double-stranded (ds) RNA-dependent protein kinase (PKR) in macrophage activation was examined. dsRNA [polyinosinic:polycytidylic acid (poly IC)]-stimulated inducible nitric oxide synthase, interleukin (IL)-1 alpha and IL-1 beta mRNA expression, nitrite formation and IL-1 release are attenuated in RAW264.7 cells stably expressing dominant negative (dn) mutants of PKR. The transcriptional regulator nuclear factor (NF)-kappa B is activated by dsRNA, and appears to be required for dsRNA-induced macrophage activation. While dnPKR mutants prevent macrophage activation, they fail to attenuate dsRNA-induced I kappa B degradation or NF-kappa B nuclear localization. The inhibitory actions of dnPKR on dsRNA-induced macrophage activation can be overcome by treatment with interferon (IPN)-gamma, an event associated with PKR degradation. Furthermore, dsRNA + IFN-gamma stimulate inducible nitric oxide synthase expression, I kappa B degradation and NF-kappa B nuclear localization to similar levels in macrophages isolated from PKR-/- and PKR+/+ mice. These findings indicate that both NF-kappa B and PKR are required for dsRNA-induced macrophage activation; however, dsRNA-induced NF-kappa B activation occurs by PKR-independent mechanisms in macrophages, In addition, the PKR dependence of dsRNA-induced macrophage activation can be overcome by IFN-gamma.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available