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-kappa B) binding sites. We hypothesized that this effect of L-RNA is mediated by RNA-dependent protein kinase (PKR) through NF-kappa B activation. We found that L-RNA activates PKR and induces NF-kappa B activation through degradation of its inhibitor I-kappa B alpha. 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.
De Lucca
Fernando L
FL
Department of Biochemistry and Immunology, School of Medicine University of São Paulo 14049-900, Ribeirão Preto, S.P., Brazil. fldlucca@fmrp.usp.br
Serrano
Sergio V
SV
Souza
Liliana R
LR
Watanabe
Maria Angelica E
MA
D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000096:biosynthesis*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D022661:RNA, Untranslated / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D019892:eIF-2 Kinase / Q000378:metabolism*
D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D022661:RNA, Untranslated; D019892:eIF-2 Kinase