Activation of RNA-dependent protein kinase and nuclear factor-kB by regulatory RNA from lipopolysaccharide-stimulated macrophages: implications for cytokine production

Our previous results showed that L-RNA, extracted from lipopolysaccharide-stimulated macrophages, induces interleukin-1, interleukin-8 and tumor necrosis factor-alpha (TNF-alpha) in resident macrophages. It was demonstrated the promoter of these cytokine genes contain nuclear factor-kB (NF-kappaB) binding sites. We hypothesized that this effect of L-RNA is mediated by RNA-dependent protein kinase (PKR) through NF-kappaB activation. We found that L-RNA activates PER and induces NF-kappaB activation through degradation of its inhibitor I-kappaBalpha. These data support the idea that L-RNA acts as a regulatory RNA. A model for the mechanism of action of L-RNA is proposed. (C) 2002 Elsevier Science B.V All rights reserved.