{"database":"Cell Collective","file_versions":[],"scores":null,"additional":{"omics_type":["Models"],"submitter":["Tomas Helikar"],"version_name":[""],"full_dataset_link":["https://cellcollective.org/#2314/il6-signalling"],"model_score":["32.0165"],"default_version":["1"],"ModelFormat":["SBML"],"submitter_affiliation":[""],"submitter_email":[""],"version_id":["1"],"repository":["Cell Collective"],"version_url":["https://cellcollective.org/#2314:1/il6-signalling"],"version_description":[""],"pubmed_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."],"pubmed_title":["Large-scale network models of IL-1 and IL-6 signalling and their hepatocellular specification."],"pubmed_authors":["Ryll Anke A, Samaga Regina R, Schaper Fred F, Alexopoulos Leonidas G LG, Klamt Steffen S"],"description_synonyms":["Myeloid Differentiation-Inducing Protein, CDF, PRKBA, Akt/PKB, Myeloid, Metastasis, acetylglucosaminyltransferase-like protein, DAKT1/PKB, Hepatocyte-Stimulating Factor, Physical, Visible Light, neoplasm metastasis, AKT1, CG17228, Social Controls, 1135/09, trauma, 1135/07, B Cell, Physiological Concepts, B Cell Stimulatory Factor 2, entry into host via enzymatic degradation of host cuticle, Macrophage Cell Factor, responsivity, 0451/09, Interferon beta-2, Dp38, Hybridoma growth factor, Analysis, myd, Mpk34C, p38B, 0244/09, Su(var)3-103, plant tissue colonization, like-acetylglucosaminyltransferase, Analyses, plant peltate hair, DROPROSA, Tissue, Mbp-1, Dm p38b, RacPK, Social, 671/2, B Cell Differentiation Factor 2, interleukin-6 receptor ligand, Phenomenas, invasive growth, Documentations, ESTS:186F5S, Physiological, single organism signaling, Radiation, UNQ391/PRO726, Injury and Wounds, Physical Traumas, Light, HSF, Su-var(3)103, invasion of other organism, BSF2, AKT/PKB, LIGHT, mKIAA0609, 1316/02, BcDNA:HL08040, IL1F2, p-Akt, simple tissue, Differentiation Factor-2, Physiological Phenomenon, Mitogen-Activated Protein Kinase p38, fg, LGR8, Lgr8, HVEML, Bacterial Diseases, 1167/13, bacterial, Controls, dAKT/dPKB, PKB/dAKT, human, MDC1D, enr, Cells, Research-Related Injuries, l(1)16Fg, Feedbacks, 0989/01, pds, RAC-ALPHA, Regulations, Research Related Injuries, D-p38 MAPK, DmelCG4006, Bacterial Disease, entry into cell of other organism involved in symbiotic interaction, Processes, B-cell hybridoma growth factor, peltate hair, p38 Protein Kinase, Jil-1, 0763/13, Injuries and Wounds, LARGE1, Human, Ly113, DmelCG17228, Wounds, IL1-BETA, IR, Insulin, p38 MAPK, host tissue colonization, Growth Factor, Prosp, CTL differentiation factor, response to IL-6, Man, p38beta, F15E12_6, network topology analysis, Injury, Differentiation Factor, MDDGB6, Hybridoma Growth Factor, p38Kb, l(3)rH013, Prodos, Su-var(3)1, AKT, Akt, Hepatic, p38 Mitogen Activated Protein Kinase, species, TR2, tumor metastasis, GPR106, 0671/02, Dp38b, l(3)j12C8, akt, Metastases, DAkt1, DAKT1, CD258, Cell, Concept, Metastase, l(3)rL433, Drug resistance to insulin (disorder), PKB, Cytokine, l(3)rI160, CWS6, 0441/16, Social Control, traumatic injury, Wounds and Injury, IFN-beta-2, Trauma, PKB-ALPHA, Neoplasm, Resistance, feed, BSF-2, CG4006, MAP Kinase, scales, p38 beta, ATCMPG1, MET, ATCMPG2, Dakt1, Bacterial, other organism invasion, HVEM-L, Interleukin HP-1, wound, signalling, l(3)rK204, dAkt/PKB, INSL3R., Epidermal Cell Derived Thymocyte Activating Factor, B Cell Differentiation Factor, entry into host cell via penetration peg, Photoradiations, signalling process, like-glycosyltransferase, p38 Mitogen-Activated Protein Kinase, B-Cell Stimulatory Factor 2, regulation, Data Analyses, Differentiation-Inducing Protein, l(3)rK137, B-Cell Stimulatory Factor-2, scale tissue, Wound, Il-6, Mbp1, Epidermal Cell Derived Thymocyte-Activating Factor, Hepatocyte, Neoplasm Metastases, Body fails to respond to insulin, D-p38, injury, cancer metastasis, B-cell stimulatory factor 2, mAb2A, IL-1, Hepatic Cell, IL-6, Concepts, Phenomenon, Formal Social Controls, Research-Related, entry into host via a specialized structure during symbiotic interaction, Immune Processes, Immune Responses, Man (Taxonomy), Biology, MUB3_18, Physiological Concept, MUB3.18, l(3)j6E2, PKB|Akt, il1b-A, GREAT, 0320/10, TNFSF14, DMPROSPER, Immune, tissue invasion, Dmp38b, signaling process, Great, associated, p38 MAP Kinase, Insulin Sensitivity, T Helper Factor, single-organism behavior, Physiological Process, wide/broad, dakt, l(3)rO534, Process, gyltl1b-b, PRO, Pro, Modern, entry into cell of other organism during symbiotic interaction, B Cell Stimulatory Factor-2, beta-2, infections, l(3)89Bq, CYS, results, D-p38b, Hepatic Cells, Interferon beta 2, invasion into other organism, PKB/Akt, PKB/AKT, PROS-1, PROS-2, dAkt, dAKT, pro, MDDGA6, MAPK, entry into host through host barriers, Physical Trauma, KIAA0609, DAkt, and GLY protein 2, acetylglucosaminyltransferase-like 1A, l(3)04226, Lymphocyte Activating Factor, Visible Radiations, DPKB, Differentiation Factor 2, Epistemology, and GLY protein 1, Visible Radiation, Interleukin, JIL1, Jil1, gyltl1b, pAkt, Voila, 0664/07, mdc1d, Control, p38, TAF[[II]], Plasmacytoma, LARGE_HUMAN, Mitogen Activated Protein Kinase p38, data analysis, IFNB2, wide, Dakt, JIL, Plasmacytoma Growth Factor, dPKB, p38 SAPK, Research-Related Injury, 186F5S, Interferon, Regulation, Physiological Processes, Protein Kinase, DRAC-PK85, biological signaling, human being, Su(var)3-1, CG7393, entry into other organism during symbiotic interaction, B-Cell, B-Cell Differentiation Factor, interleukin-1 receptor ligand, broad, froggy, Gyltl1a, l(3)10419, dmTAF8, Dpkb, dp38b, HGF, Homo sapiens, Hepatocyte Stimulating Factor, HL-VIII, anon-WO0118547.379, anon-WO0140519.15, F15E12.6, IL-1B, reactivity, PROS, tumor cell migration, 0585/13, Bacterial Infection, Gpr106, entry into other organism involved in symbiotic interaction, Infections, Interleukin I, Interleukin 6, CG7128, penetration into host via a specialized structure, metastasis, LARGE, RXFPR2, Interleukin 1, entry into host via enzymatic degradation of host anatomical structure, Visible, BPFD#36, prod, MSK, Immune Response, data processing, CG6297, Traumas, DRAC-PK, IL6, Sensitivity, TAF, 0563/18, Immune Process, p38 Mitogen Activated Protein Kinases, 2Ab17, MGI-2, Formal Social Control, anon-sts23, Myeloid Differentiation Inducing Protein, DmelCG7393, l(3)rJ806, Pros, Systems, Phenomena, Infection, TFIID, D-Akt, DmelCG6297, B-Cell Differentiation Factor-2, Radiations, IFN-beta 2, scale, akt1, dAkt1, DRAC-PK66, Photoradiation, LGR8.1, Injuries, LTg, dakt1, DmelCG7128, Hybridoma, Data, Modern Man, PKBalpha, Response, penetration into host via a specialized structure during symbiotic interaction, dAKT1, BG:DS00797.3, RAC, Rac, Lymphocyte-Activating Factor, response, TAF8, glycosyltransferase-like protein LARGE1"],"pubmed_title_synonyms":["Differentiation-Inducing Protein, Myeloid Differentiation-Inducing Protein, B-Cell Stimulatory Factor-2, scale tissue, CDF, biological signaling, Su(var)3-1, Myeloid, acetylglucosaminyltransferase-like protein, Il-6, peltate hair, B-cell hybridoma growth factor, Hepatocyte-Stimulating Factor, Mbp1, Epidermal Cell Derived Thymocyte-Activating Factor, B-Cell, Jil-1, B-Cell Differentiation Factor, interleukin-1 receptor ligand, LARGE1, froggy, Gyltl1a, B-cell stimulatory factor 2, mAb2A, B Cell, B Cell Stimulatory Factor 2, IL-1, HGF, Macrophage Cell Factor, IL1-BETA, IL-6, Hepatocyte Stimulating Factor, anon-WO0118547.379, Interferon beta-2, Hybridoma growth factor, Growth Factor, CTL differentiation factor, myd, IL-1B, Su(var)3-103, Differentiation Factor, like-acetylglucosaminyltransferase, MDDGB6, plant peltate hair, Hybridoma Growth Factor, Interleukin I, Interleukin 6, Mbp-1, LARGE, Interleukin 1, il1b-A, B Cell Differentiation Factor 2, BPFD#36, MSK, interleukin-6 receptor ligand, Su-var(3)1, CG6297, signaling process, IL6, T Helper Factor, single organism signaling, signalling., 2Ab17, MGI-2, gyltl1b-b, B Cell Stimulatory Factor-2, beta-2, Myeloid Differentiation Inducing Protein, HSF, Su-var(3)103, BSF2, Interferon beta 2, MDDGA6, mKIAA0609, IFN-beta-2, IL1F2, BSF-2, scales, Differentiation Factor-2, KIAA0609, acetylglucosaminyltransferase-like 1A, DmelCG6297, Lymphocyte Activating Factor, B-Cell Differentiation Factor-2, fg, IFN-beta 2, Differentiation Factor 2, JIL1, gyltl1b, Jil1, scale, mdc1d, Interleukin HP-1, LARGE_HUMAN, Plasmacytoma, MDC1D, IFNB2, Epidermal Cell Derived Thymocyte Activating Factor, B Cell Differentiation Factor, like-glycosyltransferase, enr, Hybridoma, signalling process, JIL, Plasmacytoma Growth Factor, B-Cell Stimulatory Factor 2, Lymphocyte-Activating Factor, Interferon, glycosyltransferase-like protein LARGE1"],"name_synonyms":["Differentiation-Inducing Protein, signalling., Myeloid Differentiation-Inducing Protein, B-Cell Stimulatory Factor-2, CDF, biological signaling, MGI-2, Myeloid, Il-6, B-cell hybridoma growth factor, Hepatocyte-Stimulating Factor, B-Cell, B Cell Stimulatory Factor-2, beta-2, Myeloid Differentiation Inducing Protein, B-Cell Differentiation Factor, HSF, B-cell stimulatory factor 2, B Cell, BSF2, Interferon beta 2, B Cell Stimulatory Factor 2, HGF, IFN-beta-2, IL-6, Hepatocyte Stimulating Factor, Interferon beta-2, BSF-2, Hybridoma growth factor, Growth Factor, Differentiation Factor-2, CTL differentiation factor, B-Cell Differentiation Factor-2, IFN-beta 2, Differentiation Factor 2, Differentiation Factor, Hybridoma Growth Factor, Interleukin 6, Interleukin HP-1, Plasmacytoma, B Cell Differentiation Factor 2, IFNB2, interleukin-6 receptor ligand, B Cell Differentiation Factor, Hybridoma, signalling process, Plasmacytoma Growth Factor, signaling process, B-Cell Stimulatory Factor 2, IL6, Interferon, single organism signaling"],"pubmed_abstract_synonyms":["Myeloid Differentiation-Inducing Protein, CDF, PRKBA, Akt/PKB, Myeloid, Metastasis, acetylglucosaminyltransferase-like protein, DAKT1/PKB, Hepatocyte-Stimulating Factor, Physical, Visible Light, neoplasm metastasis, AKT1, CG17228, Social Controls, 1135/09, trauma, 1135/07, B Cell, Physiological Concepts, B Cell Stimulatory Factor 2, entry into host via enzymatic degradation of host cuticle, Macrophage Cell Factor, responsivity, 0451/09, Interferon beta-2, Dp38, Hybridoma growth factor, Analysis, myd, Mpk34C, p38B, 0244/09, Su(var)3-103, plant tissue colonization, like-acetylglucosaminyltransferase, Analyses, plant peltate hair, DROPROSA, Tissue, Mbp-1, Dm p38b, RacPK, Social, 671/2, B Cell Differentiation Factor 2, interleukin-6 receptor ligand, Phenomenas, invasive growth, Documentations, ESTS:186F5S, Physiological, single organism signaling, Radiation, UNQ391/PRO726, Injury and Wounds, Endogenous, Physical Traumas, Light, HSF, Su-var(3)103, invasion of other organism, BSF2, AKT/PKB, LIGHT, mKIAA0609, 1316/02, BcDNA:HL08040, IL1F2, p-Akt, simple tissue, Differentiation Factor-2, Physiological Phenomenon, Mitogen-Activated Protein Kinase p38, fg, LGR8, Lgr8, HVEML, Bacterial Diseases, 1167/13, bacterial, Controls, dAKT/dPKB, PKB/dAKT, human, MDC1D, enr, Cells, Research-Related Injuries, Regeneration, l(1)16Fg, Feedbacks, 0989/01, pds, RAC-ALPHA, Regulations, Research Related Injuries, D-p38 MAPK, DmelCG4006, Bacterial Disease, entry into cell of other organism involved in symbiotic interaction, Processes, B-cell hybridoma growth factor, peltate hair, p38 Protein Kinase, Jil-1, 0763/13, Injuries and Wounds, LARGE1, Human, Ly113, DmelCG17228, Wounds, IL1-BETA, IR, Insulin, p38 MAPK, host tissue colonization, Growth Factor, Prosp, CTL differentiation factor, response to IL-6, Man, p38beta, F15E12_6, network topology analysis, Injury, Differentiation Factor, MDDGB6, Hybridoma Growth Factor, p38Kb, l(3)rH013, Prodos, Su-var(3)1, AKT, Akt, Hepatic, p38 Mitogen Activated Protein Kinase, species, TR2, tumor metastasis, GPR106, 0671/02, Dp38b, l(3)j12C8, akt, Metastases, DAkt1, DAKT1, CD258, Cell, Concept, Metastase, l(3)rL433, Drug resistance to insulin (disorder), PKB, Cytokine, l(3)rI160, CWS6, 0441/16, Social Control, traumatic injury, Wounds and Injury, IFN-beta-2, Trauma, PKB-ALPHA, Neoplasm, Resistance, feed, BSF-2, CG4006, MAP Kinase, scales, p38 beta, ATCMPG1, MET, ATCMPG2, Dakt1, Bacterial, Regenerations, other organism invasion, HVEM-L, Interleukin HP-1, wound, signalling, l(3)rK204, dAkt/PKB, INSL3R., Epidermal Cell Derived Thymocyte Activating Factor, B Cell Differentiation Factor, entry into host cell via penetration peg, Photoradiations, signalling process, like-glycosyltransferase, p38 Mitogen-Activated Protein Kinase, B-Cell Stimulatory Factor 2, regulation, Data Analyses, Differentiation-Inducing Protein, l(3)rK137, B-Cell Stimulatory Factor-2, scale tissue, Wound, Il-6, Mbp1, Epidermal Cell Derived Thymocyte-Activating Factor, Hepatocyte, Neoplasm Metastases, Body fails to respond to insulin, D-p38, injury, cancer metastasis, B-cell stimulatory factor 2, mAb2A, IL-1, Hepatic Cell, IL-6, Concepts, Phenomenon, Formal Social Controls, Research-Related, entry into host via a specialized structure during symbiotic interaction, Immune Processes, Immune Responses, Man (Taxonomy), Biology, MUB3_18, Physiological Concept, MUB3.18, l(3)j6E2, PKB|Akt, il1b-A, GREAT, 0320/10, TNFSF14, DMPROSPER, Immune, tissue invasion, Dmp38b, signaling process, Great, associated, p38 MAP Kinase, Insulin Sensitivity, T Helper Factor, single-organism behavior, Physiological Process, wide/broad, dakt, l(3)rO534, Process, gyltl1b-b, PRO, Pro, Modern, entry into cell of other organism during symbiotic interaction, B Cell Stimulatory Factor-2, beta-2, infections, l(3)89Bq, CYS, results, D-p38b, Hepatic Cells, Interferon beta 2, invasion into other organism, PKB/Akt, PKB/AKT, PROS-1, PROS-2, dAkt, dAKT, pro, MDDGA6, MAPK, entry into host through host barriers, Physical Trauma, KIAA0609, DAkt, and GLY protein 2, acetylglucosaminyltransferase-like 1A, l(3)04226, Lymphocyte Activating Factor, Visible Radiations, DPKB, Differentiation Factor 2, Epistemology, and GLY protein 1, Visible Radiation, Interleukin, JIL1, Jil1, gyltl1b, pAkt, Voila, 0664/07, mdc1d, Control, p38, TAF[[II]], Plasmacytoma, LARGE_HUMAN, Mitogen Activated Protein Kinase p38, data analysis, IFNB2, wide, Endogenous Regeneration, Dakt, JIL, Plasmacytoma Growth Factor, dPKB, p38 SAPK, Research-Related Injury, 186F5S, Interferon, Regulation, Physiological Processes, Protein Kinase, DRAC-PK85, biological signaling, human being, Su(var)3-1, CG7393, entry into other organism during symbiotic interaction, B-Cell, B-Cell Differentiation Factor, interleukin-1 receptor ligand, broad, froggy, Gyltl1a, l(3)10419, dmTAF8, Dpkb, dp38b, HGF, Homo sapiens, Hepatocyte Stimulating Factor, HL-VIII, anon-WO0118547.379, anon-WO0140519.15, F15E12.6, IL-1B, reactivity, PROS, tumor cell migration, 0585/13, Bacterial Infection, Gpr106, entry into other organism involved in symbiotic interaction, Infections, Interleukin I, Interleukin 6, CG7128, penetration into host via a specialized structure, metastasis, LARGE, RXFPR2, Interleukin 1, entry into host via enzymatic degradation of host anatomical structure, Visible, BPFD#36, prod, MSK, Immune Response, data processing, CG6297, Traumas, DRAC-PK, IL6, Sensitivity, TAF, 0563/18, Immune Process, p38 Mitogen Activated Protein Kinases, 2Ab17, MGI-2, Formal Social Control, anon-sts23, Myeloid Differentiation Inducing Protein, DmelCG7393, l(3)rJ806, Pros, Systems, Phenomena, Infection, TFIID, D-Akt, DmelCG6297, B-Cell Differentiation Factor-2, Radiations, IFN-beta 2, scale, akt1, dAkt1, DRAC-PK66, Photoradiation, LGR8.1, Injuries, LTg, dakt1, DmelCG7128, Hybridoma, Data, Modern Man, PKBalpha, Response, penetration into host via a specialized structure during symbiotic interaction, dAKT1, BG:DS00797.3, RAC, Rac, Lymphocyte-Activating Factor, response, TAF8, glycosyltransferase-like protein LARGE1"],"additional_accession":[]},"is_claimable":false,"name":"IL-6 Signalling","description":"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 regenerationvs. 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.","dates":{"created":"2014-01-11","publication":"","submission":"2017-05-18","last_modified":"2017-05-18"},"accession":"2314","cross_references":{"pubmed":["21968890"]}}