%0 Journal Article
%T Drotregocin alfa (activated) inhibits degradation of cytokine-mRNA in an endothelial model of inflammation
%A M Brueckmann
%A HM Weiler
%A V Liebe
%A A Marx
%A U Hoffmann
%A S Lang
%A C Liebetrau
%A M Borggrefe
%A KK Haase
%A G Huhle
%J Critical Care
%D 2003
%I BioMed Central
%R 10.1186/cc1908
%X rhAPC (2.5每20 米g/ml) upregulated the amount of MCP-1-mRNA and IL-8-mRNA and caused a time-dependent and dose-dependent increase in MCP-1-, IL-6- and IL-8-protein production (P < 0.001 for rhAPC 5 米g/ml at 4每24 hours) in HUVEC. Experiments were conducted to evaluate the effect of rhAPC on mRNA degradation and mRNA stability independently of its possible effects on gene transcription. After stimulation of mRNA transcription by TNF-alpha (0.1每1 ng/ml) for 3 hours, HUVEC were treated with actinomycin D (1 米g/ml), preventing new synthesis of transcript, in the presence or absence of rhAPC. HUVEC receiving rhAPC contained more MCP-1-mRNA and IL-8-mRNA after 1 hour and up to 8 hours than controls, suggesting an inhibitory effect of rhAPC on mRNA degradation. Electrophoretic mobility shift assays (EMSA) revealed that APC attenuated NF-百B activity implying that NF-百B may not be involved in the upregulatory effect of rhAPC on MCP-1, IL-6 and IL-8 production.The ability of APC to upregulate the production of MCP-1, IL-6 and IL-8, most likely by increasing the stability of MCP-1-mRNA rather than by transcriptional activation via NF-百B, identifies a novel post-transcriptional pathway, by which APC may control the local inflammatory reaction, thereby modulating the extent of endothelial injury.
%U http://ccforum.com/content/7/S2/P019