Large-scale network models of IL-1 and IL-6 signalling and their hepatocellular specification

Ryll, A; Samaga, R; Schaper, F; Alexopoulos, LG; Klamt, S

dc.contributor.author	Ryll, A	en
dc.contributor.author	Samaga, R	en
dc.contributor.author	Schaper, F	en
dc.contributor.author	Alexopoulos, LG	en
dc.contributor.author	Klamt, S	en
dc.date.accessioned	2014-03-01T01:35:54Z
dc.date.available	2014-03-01T01:35:54Z
dc.date.issued	2011	en
dc.identifier.issn	1742-206X	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/21247
dc.subject.classification	Biochemistry & Molecular Biology	en
dc.subject.other	cytokine	en
dc.subject.other	interleukin 1	en
dc.subject.other	interleukin 6	en
dc.subject.other	mitogen activated protein kinase p38	en
dc.subject.other	article	en
dc.subject.other	biological model	en
dc.subject.other	human	en
dc.subject.other	liver cell	en
dc.subject.other	metabolism	en
dc.subject.other	physiology	en
dc.subject.other	protein protein interaction	en
dc.subject.other	signal transduction	en
dc.subject.other	systems biology	en
dc.subject.other	Cytokines	en
dc.subject.other	Hepatocytes	en
dc.subject.other	Humans	en
dc.subject.other	Interleukin-1	en
dc.subject.other	Interleukin-6	en
dc.subject.other	MAP Kinase Signaling System	en
dc.subject.other	Metabolic Networks and Pathways	en
dc.subject.other	Models, Biological	en
dc.subject.other	p38 Mitogen-Activated Protein Kinases	en
dc.subject.other	Protein Interaction Maps	en
dc.subject.other	Systems Biology	en
dc.subject.other	Bacteria (microorganisms)	en
dc.title	Large-scale network models of IL-1 and IL-6 signalling and their hepatocellular specification	en
heal.type	journalArticle	en
heal.identifier.primary	10.1039/c1mb05261f	en
heal.identifier.secondary	http://dx.doi.org/10.1039/c1mb05261f	en
heal.language	English	en
heal.publicationDate	2011	en
heal.abstract	The pro-inflammatory cytokines interleukin 1 (IL-1) and 6 (IL-6) are crucially involved in the regulation of a multitude of physiological processes, in particular coordinating the immune response upon bacterial infection and tissue injury. Both interleukins induce complex signalling cascades and trigger the production of mitogenic, pro-proliferative, anti-apoptotic, chemotactic, and pro-angiogenic factors thereby affecting the delicate balance between regeneration vs. invasive growth, tumourigenesis and metastasis. Moreover, several links to insulin resistance have been found within their associated signalling networks. Focusing on this from a systems biology perspective, we introduce comprehensive large-scale network models of IL-1 and IL-6 signalling which are based on a logical modelling approach and reflect the current biological knowledge. Theoretical network analysis enabled us to uncover general topological features and to make testable predictions on the stimulus-response behaviour of the networks. In this context, non-intuitive network-wide species dependencies as well as structures of regulatory feedback and feed-forward mechanisms could be characterised. By integrating high-throughput phosphoproteomic data from primary human hepatocytes we optimised the model structures to obtain models with high prediction accuracy for hepatocytes. Our model-based data analysis, for instance, suggested model modifications regarding (i) Akt contribution to IL-1-stimulated p38 MAPK activation and (ii) insignificant p38 MAPK activation in response to IL-6. In light of the presented results and in conjunction with the detailed model documentations, both models hold great potential for theoretical studies and practical applications. © 2011 The Royal Society of Chemistry.	en
heal.publisher	ROYAL SOC CHEMISTRY	en
heal.journalName	Molecular BioSystems	en
dc.identifier.doi	10.1039/c1mb05261f	en
dc.identifier.isi	ISI:000296648800009	en
dc.identifier.volume	7	en
dc.identifier.issue	12	en
dc.identifier.spage	3253	en
dc.identifier.epage	3270	en