IL-6 is a central mediator of the immediate induction of hepatic acute phase proteins (APP) in the liver during infection and after injury, but increased IL-6 activity has been associated with multiple pathological conditions. In hepatocytes, IL-6 activates JAK1-STAT3 signaling that induces the negative feedback regulator SOCS3 and expression of APPs. While different inhibitors of IL-6-induced JAK1-STAT3-signaling have been developed, understanding their precise impact on signaling dynamics requires a systems biology approach.
View Article and Find Full Text PDFObjective: Bone morphogenetic protein (BMP)-9, a member of the transforming growth factor-β family of cytokines, is constitutively produced in the liver. Systemic levels act on many organs and tissues including bone and endothelium, but little is known about its hepatic functions in health and disease.
Design: Levels of BMP-9 and its receptors were analysed in primary liver cells.
Systemic iron levels must be maintained in physiological concentrations to prevent diseases associated with iron deficiency or iron overload. A key role in this process plays ferroportin, the only known mammalian transmembrane iron exporter, which releases iron from duodenal enterocytes, hepatocytes, or iron-recycling macrophages into the blood stream. Ferroportin expression is tightly controlled by transcriptional and post-transcriptional mechanisms in response to hypoxia, iron deficiency, heme iron and inflammatory cues by cell-autonomous and systemic mechanisms.
View Article and Find Full Text PDFThe induction of suppressor of cytokine signalling (SOCS)3 expression context dependently involves regulation of SOCS3 transcript stability as previously demonstrated for MAPK activated protein kinase (MK)2-dependent regulation of SOCS3 expression by TNFα (Ehlting et al., 2007). In how far the IL-6-type cytokine OSM, which in contrast to IL-6 is a strong activator of p38(MAPK)/MK2 signalling, also involves regulation of transcript stability and activation of MK2 to induce SOCS3 expression is unclear.
View Article and Find Full Text PDFThe Argonaute proteins play essential roles in development and cellular metabolism in many organisms, including plants, flies, worms, and mammals. Whereas in organisms such as Caenorhabditis elegans and Arabidopsis thaliana, creation of Argonaute mutant strains allowed the study of their biological functions, in mammals the application of this approach is limited by its difficulty and in the specific case of Ago2 gene, by the lethality of such mutation. Hence, in human cells, functional studies of Ago proteins relied on phenotypic suppression using small interfering RNA (siRNA) which involves Ago proteins and the RNA interference mechanism.
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