Gene interactions and pathways from curated databases and text-mining

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IL6 — SOCS3

Pathways - manually collected, often from reviews:

Text-mined interactions from Literome

Lebel et al., Endocrinology 2000 (Endotoxemia) : The endothelium of the brain capillaries also exhibited up-regulation of both IL-6 receptor and gp130 subunits during systemic inflammation, which allowed SOCS-3 expression in response to circulating IL-6
Bode et al., Biol Chem 2001 (Carcinoma, Hepatocellular) : Accordingly, overexpression of a constitutively active MKK6 in HepG2 cells enhanced basal activity or IL-6 induced transcriptional activation of a SOCS3 promoter reporter construct, whereas overexpression of a dominant negative mutant of MKK6 downregulated the IL-6 mediated activation of the SOCS3 promoter ... These data indicate that p38MAPK-activation is crucial for IL-6 induced SOCS3 expression and downregulation of IL-6 mediated gene induction
Berlato et al., J Immunol 2002 (MAP Kinase Signaling System) : Herein, we show that stable transfection of SOCS-3 into the mouse macrophage cell line J774 resulted in an inhibition of NO, TNF-alpha, IL-6 , and GM-CSF secretion in response to LPS at levels similar to those exerted by IL-10 in LPS stimulated wild-type J774 ... Constitutive SOCS-3 expression also down-regulated the mRNA expression of inducible NO synthase and IL-6 and impaired the production of TNF-alpha, mainly at a post-transcriptional level
Croker et al., Nat Immunol 2003 : SOCS3 negatively regulates IL-6 signaling in vivo
Yasukawa et al., Nat Immunol 2003 : SOCS3 specifically prevents activation of STAT3 by IL-6 but not IL-10
Bode et al., J Immunol 2003 : Recently, it has been demonstrated that TNF-alpha and LPS induce the expression of suppressor of cytokine signaling 3 ( SOCS3 ) and inhibit IL-6 induced STAT3 activation in macrophages
Yang et al., J Biol Chem 2004 : Dual function of interleukin-1beta for the regulation of interleukin-6 induced suppressor of cytokine signaling 3 expression ... Herein we analyzed IL-1beta mediated regulation of IL-6 induced expression of the feedback inhibitor SOCS3 ... Such a regulatory network allows IL-1beta to counteract IL-6 dependent expression of acute-phase protein genes without inhibiting IL-6 induced SOCS3 expression and provides a reasonable mechanism for the IL-1beta dependent inhibition of acute-phase gene induction, because reduced SOCS3 expression would lead to enhanced IL-6 activity
Rieusset et al., Diabetes 2004 (Diabetes Mellitus...) : IL-6 inhibited insulin signaling and induced SOCS-3 expression in differentiated myotubes ... In subcutaneous adipose tissue, SOCS-3 mRNA levels were increased in obese individuals and strongly correlated with IL-6 expression, supporting a paracrine effect of IL-6 on SOCS-3 expression in fat
Ehlting et al., Biochem J 2005 : In the present study, we show that mutation of this GC-rich element abolishes IL-6 dependent transcriptional activation of the SOCS3 promoter and that Sp3 ( specificity protein 3 ), a ubiquitously expressed transcription factor, but not Sp1 binds to this GC-rich motif, suggesting that Sp3 is involved in the regulation of SOCS3 expression ... The results suggest that Sp3 is important for IL-6 induced transcriptional activation of the SOCS3 ( gene ) promoter and acts as an enhancer of basal as well as induced transcriptional activity, resulting in enhanced SOCS3 mRNA and protein expression
Sommer et al., J Biol Chem 2005 : We set out to investigate whether SOCS3 phosphorylation may play a role in IL-6 signaling ... Using Src and Janus kinase inhibitors as well as Src kinase-deficient mouse embryonic fibroblasts, we provide evidence that Src kinases, which we found to be constitutively active in these cells, are involved in the phosphorylation of IL-6 induced SOCS3 ... In addition, we found that receptor-tyrosine kinases such as platelet derived growth factor receptor or epidermal growth factor receptor can very potently phosphorylate IL-6 induced SOCS3
Yang et al., J Hepatol 2005 (Disease Models, Animal...) : Interleukin-6 plays a crucial role in the hepatic expression of SOCS3 during acute inflammatory processes in vivo ... However, several signaling pathways converge on SOCS3 : SOCS3 can be induced by other mediators in vitro, and it does not exclusively inhibit IL-6 signaling ... Using IL-6-deficient mice we analyzed the role of interleukin-6 for the hepatic SOCS3 expression in response to turpentine and LPS as models of aseptic and bacterial inflammation, respectively ... Our data strongly argue for a crucial role of IL-6 in the hepatic expression of SOCS3 during acute inflammatory processes in vivo
Spangenburg et al., J Physiol 2006 : SOCS-3 overexpression increased IL-6 transcriptional activity by 15-fold, however, when the NF-kappaB site was mutated SOCS-3 failed to increase IL-6 transcriptional activity
Rakshit et al., J Bone Joint Surg Am 2006 (Osteolysis) : Titanium and polymethylmethacrylate also both induced expression of SOCS3 , an inhibitor of interleukin-6 signaling ... Wear particle inhibition of interleukin-6 specifically involves the activation of p38 mitogen activated protein kinase and is accompanied by substantial induction of SOCS3 , an inhibitor of interleukin-6 signaling
Stumhofer et al., Nat Immunol 2006 (Encephalitis...) : In vitro, treatment of naive primary T cells with IL-27 suppressed the development T ( H ) -17 cells induced by IL-6 and transforming growth factor-beta, which was dependent on the intracellular signaling molecule STAT1 but was independent of inhibition of IL-6 signaling mediated by the suppressor protein SOCS3
Pietrangelo et al., Gastroenterology 2007 : IL-6 stimulated phospho STAT3, serum amyloid A (SAA), and suppressor of cytokine signaling 3 ( SOCS3 ) expression in livers of wild-type and alfpCregp130 ( Y757F/LoxP ) mice, whereas this response was blocked in alfpCre gp130 ( LoxP/LoxP ) and alfpCre gp130 ( DeltaSTAT/LoxP ) mice
Isomoto et al., Gastroenterology 2007 (Bile Duct Neoplasms...) : Treatment with a demethylating agent, 5-aza-2'-deoxycytidine ( DAC ), restored IL-6 induction of SOCS-3 , terminated the phospho-STAT-3 response, and reduced cellular levels of Mcl-1 ... Enforced expression of SOCS-3 also reduced IL-6 induction of phospho-STAT-3 and Mcl-1
Boyle et al., J Reprod Immunol 2008 : The creation of mice with conditional deletion of SOCS3 in different tissues has also uncovered critical roles for SOCS3 in the regulation of IL-6 , G-CSF and leptin signalling
Kim et al., J Biol Chem 2008 (Carcinoma, Hepatocellular...) : Furthermore, IL-6 induced SOCS3 expression is inhibited by rapamycin, and ectopic expression of SOCS3 blocks the ability of rapamycin to enhance insulin sensitivity in the presence of IL-6
Yu et al., Int J Biochem Cell Biol 2008 : SOCS 3 and PPAR-gamma ligands inhibit the expression of IL-6 and TGF-beta1 by regulating JAK2/STAT3 signaling in pancreas
Uno et al., Horm Metab Res 2008 : These results suggest that the IL-1alpha mediated deterioration of insulin signaling is largely due to the IL-6 production and SOCS3 induction in 3T3-L1 adipocytes
Yarwood et al., J Biol Chem 2008 : Secondly, knockdown of C/EBPbeta and -delta isoforms abolished both SOCS-3 induction and inhibition of IL-6 signaling in response to cAMP
Kiu et al., Growth Factors 2007 : Analysis of suppressor of cytokine signalling 3 ( SOCS3 ) -deficient macrophages reveal that SOCS3 is necessary but surprisingly, not sufficient for the complete crosstalk inhibition of IL-6 signaling induced by LPS and TNFalpha
Zhang et al., J Immunol 2008 (Multiple Sclerosis) : Our results demonstrated statin mediated increases in suppressor of cytokine secretion (SOCS) 3 and suppressor of cytokine secretion 7, which negatively regulate the STAT/JAK signal transduction pathway and IL-6 and IL-23 gene expression in monocytes
Zou et al., FEBS Lett 2008 : The role of microtubule associated protein 1S in SOCS3 regulation of IL-6 signaling
Orabona et al., Proc Natl Acad Sci U S A 2008 : We found that SOCS3-known to interact with phosphotyrosine containing peptides and be selectively induced by CD28-Ig/IL-6-would bind IDO and target the IDO/SOCS3 complex for ubiquitination and subsequent proteasomal degradation
Kageyama et al., J Endocrinol 2009 : In the present study, we examined whether SOCS-3 is regulated by IL-6 and cAMP in hypothalamic 4B cells ... Therefore, SOCS-3 , induced by a cAMP stimulant and IL-6 , would be involved in the negative regulation of CRF gene expression in hypothalamic cells
Thompson et al., J Biol Chem 2009 : Interleukin-6 , but not interleukin-10, stimulated phosphorylation of STAT3, and induction of SOCS3 mRNA expression were potentiated in a time- and dose dependent manner in macrophage cell lines derived from AFABP/aP2-EFABP/mal1 double knock-out mice relative to cells from wild type animals
Qin et al., J Immunol 2009 : TGF-beta inhibits IL-6 induced SOCS3 promoter activity in T cells
Henkel et al., Hepatology 2009 (Insulin Resistance) : IL-6 but not PGE ( 2 ) induced suppressors of cytokine signaling ( SOCS3 )
John et al., J Orthop Res 2010 : TNFalpha stimulation augmented SOCS1, whereas SOCS3 expression in tenocytes was also induced by IL-6
Ma et al., J Immunol 2010 : Moreover, we elucidated an important role for suppressor of cytokine signaling (SOCS) 3 in IL-17 enhancement of IL-6 signaling in astrocytes
Fukushima et al., J Endod 2010 : IL-1beta and IL-6 simultaneously induced IL-8 and monocyte chemoattractant protein-1 secretion in PDL cells, whereas SOCS-3 overexpression suppressed secretion of these chemokines through inhibition of phosphorylation in downstream signaling
Chang et al., J Pharmacol Sci 2011 (Carcinoma, Hepatocellular...) : Both compounds blocked suppressor of cytokine signaling 3 ( SOCS-3 ) -mRNA expression induced by IL-6
Lesina et al., Cancer Cell 2011 (Adenocarcinoma...) : Here, we establish that, in addition to oncogenic Kras ( G12D ), IL-6 transsignaling dependent activation of Stat3/Socs3 is required to promote PanIN progression and pancreatic ductal adenocarcinoma ( PDAC )
Funaoka et al., J Virol 2011 : In conclusion, HCV R70 and L91 core mutants were resistant to interferon in vitro, and the resistance may be induced by IL-6 induced upregulation of SOCS3
Serrano-Marco et al., Diabetes 2011 : In addition, this drug treatment abolished IL-6 induced SOCS3 expression in differentiated 3T3-L1 adipocytes
Scheller et al., J Cell Biochem 2011 : Inhibition of SOCS3 by ZA resulted in significant increases in IL-6 production
Al-Shanti et al., J Cell Biochem 2012 : Inhibitory effects of IL-6 on IGF-1 activity in skeletal myoblasts could be mediated by the activation of SOCS-3
Kim et al., Diabetologia 2012 (Insulin Resistance) : IL-6 induced STAT3 transactivation and SOCS3 production were significantly repressed by metformin, adenoviral constitutively active AMPK ( Ad-CA-AMPK ), and adenoviral SHP ( Ad-SHP ), but not in Shp knockdown, or with the adenoviral dominant negative form of AMPK ( Ad-DN-AMPK )
Yang et al., Curr Drug Metab 2012 : SOCS-3 , CRP, and LBP were extensively induced by IL-6 , with maximal induction observed at 2 ( SOCS-3 ) and 12 hrs ( CRP ; LBP ), demonstrating that the cultured human hepatocytes responded to IL-6 treatment
Lewkowicz et al., Immunobiology 2013 : We showed that LPS activated Treg cells promote generation of IL-10 and TGF-ß1, inhibit IL-6 production by PMNs and induce the expression of heme oxygenase-1 (HO-1) and the suppressor of cytokine signaling 3 molecule ( SOCS3 )
Rossa et al., PloS one 2012 (Carcinoma, Squamous Cell...) : Immunofluorescence and western blot were used to study the subcellular localization of endogenous SOCS3 induced by IL-6
Kleinsteuber et al., Blood 2012 (Tuberculosis) : SOCS3 promotes interleukin-17 expression of human T cells
Park et al., PloS one 2012 : In parallel to STAT3 phosphorylation, OSM and IL-6/R induce SOCS3 expression at the mRNA and protein level ... P6 treatment inhibits SOCS3 expression, indicating that STAT3 is required for OSM and IL-6/R induced SOCS3 expression
Romain et al., Arterioscler Thromb Vasc Biol 2013 (Aortic Aneurysm, Abdominal...) : Overexpression of SOCS3 in T lymphocytes leads to impaired interleukin-17 production and severe aortic aneurysm formation in mice -- brief report
Park et al., J Allergy Clin Immunol 2013 (Nasal Polyps...) : Nasal epithelial cell culture was used to elucidate the effect of IL-4, IL-5, IL-6 , IL-10, IL-13, IFN-?, TNF-a, and TGF-ß1 on SOCS1 and SOCS3 expression in sinus mucosa
Teramo et al., Blood 2013 (Leukemia, Large Granular Lymphocytic) : By treating neoplastic LGLs with a demethylating agent, IL-6 mediated SOCS3 expression was restored with consequent P-STAT3 and myeloid cell leukemia-1 down-modulation
Collins et al., PloS one 2013 : Furthermore, miR-19a mediated reduction of SOCS3 enhanced IFN-a and interleukin (IL)-6 signal transduction through STAT3
Suzuki et al., Oncogene 1998 (Leukemia, Myeloid, Acute) : In M1 myeloid leukemia cells, CIS3 was induced by neither interleukin 6 (IL6) nor interferon gamma (IFNgamma), while JAB was induced strongly by IFNgamma and slightly by IL6 and leukemia inhibitory factor (ILF)
Nicholson et al., EMBO J 1999 : SOCS-1 and SOCS-3 inhibited both interleukin-6 (IL-6)- and leukemia inhibitory factor (LIF) induced macrophage differentiation of murine monocytic leukemic M1 cells and LIF induction of a Stat3-responsive reporter construct in 293T fibroblasts