◀ Back to IL6
IL6 — STAT1
Pathways - manually collected, often from reviews:
-
NCI Pathway Database IL27-mediated signaling events:
IL6 (IL6)
→
STAT1 (dimer) complex (STAT1)
(transcription, activates)
Stumhofer et al., Nat Immunol 2006*, Batten et al., Nat Immunol 2006*
Evidence: mutant phenotype, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
STAT1 (STAT1)
(modification, activates)
Croker et al., Nat Immunol 2003, Lang et al., Nat Immunol 2003, Guschin et al., EMBO J 1995, Wegenka et al., Mol Cell Biol 1994, Lütticken et al., Science 1994, Gerhartz et al., J Biol Chem 1996
Evidence: mutant phenotype, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
STAT1 (STAT1)
(modification, activates)
Liu et al., Proc Natl Acad Sci U S A 1998
Evidence: physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
STAT1/PIAS1 complex (STAT1-PIAS1)
(modification, activates)
Liu et al., Proc Natl Acad Sci U S A 1998
Evidence: physical interaction
-
Reactome Reaction:
IL6
→
STAT1
(indirect_complex)
Decker et al., Oncogene 2000*, Gerhartz et al., J Biol Chem 1996, Hemmann et al., J Biol Chem 1996
-
Reactome Reaction:
IL6
→
STAT1
(reaction)
Zhong et al., Science 1994, Gerhartz et al., J Biol Chem 1996, Hemmann et al., J Biol Chem 1996
Text-mined interactions from Literome
Bottrel et al., Antimicrob Agents Chemother 1999
:
The immune response modifier imiquimod
requires STAT-1 for induction of interferon, interferon stimulated genes, and
interleukin-6
Subramaniam et al., Biochem Biophys Res Commun 1999
:
Immunoprecipitation with specific antibodies followed by Western blot analysis with antiphosphotyrosine antibody has shown that in U937 cells,
interleukin-17 induces time dependent stimulation of tyrosine phosphorylation of JAK 1, 2 and 3, Tyk 2 and
STAT 1 , 2, 3 and 4 within 0.5 to 30 min. Interleukin-17 mediated tyrosine phosphorylation of these proteins strongly suggests that the JAK/STAT signaling pathway may play a major role in transducing signals from interleukin-17 receptors to the nucleus
Schumann et al., J Neurochem 1999
(Neuroblastoma) :
IL-6 induced activation and translocation of STAT3 and to a lesser degree
STAT1 but not STAT5 are demonstrated
Lee et al., J Exp Med 1999
:
Interestingly,
interleukin (IL)-7 selectively
activated STAT1 and induced MHC class I in mature T but not B cells
Wu et al., J Biol Chem 2000
:
Overexpression of wild type
Stat1 protein
inhibited IL-6 activated DNA binding complexes containing Stat3 homodimers, which may explain the partial negative effect of Stat1 on IL-6 induced neurite outgrowth
Teague et al., J Exp Med 2000
:
However, there was profound inhibition of
IL-6 induced
Stat1 phosphorylation in activated T cells compared with resting T cells
Zhong et al., Mol Pharmacol 2000
:
Immunoprecipitation experiments showed that
IL-6 increased tyrosine phosphorylation of
Stat1 and Stat3 in PC12 cells, whereas NE caused a sustained increase in tyrosine phosphorylation of Stat1
Iwamoto et al., Oncogene 2000
(Acute-Phase Reaction) :
In contrast, JAB could downregulate phosphorylation of
STAT1 and STAT3
induced by interferon gamma (IFNgamma) and
interleukin-6 (IL-6) plus soluble IL6 receptor ( sIL-6R ), respectively
Shen et al., Biochem J 2000
:
Furthermore, IL-1beta selectively down-regulated the
IL-6 induced tyrosine phosphorylation of
STAT1 without affecting the level of STAT1 or tyrosine phosphorylation of STAT3 ... However, pretreatment with the proteasome inhibitor MG132 under conditions that prevented the IL-1beta dependent activation of the nuclear factor NF-kappaB also blocked the inhibitory effect of IL-1beta on
IL-6 activated
STAT1 ... In related experiments, the protein tyrosine phosphatase inhibitor Na ( 3 ) VO ( 4 ) also antagonized the inhibitory effect of IL-1beta on the
activation of
STAT1 by
IL-6
Samardzic et al., Cytokine 2001
:
STAT1 is
required for iNOS activation, but not
IL-6 production in murine fibroblasts ... These results indicate that
STAT1 activation and subsequent IRF-1 transcription are
required for induction of iNOS, but not
IL-6 in murine fibroblasts
Mitani et al., Genes Cells 2001
:
In fact,
IL-6 induced activation of the
Stat1 and Stat3 transcription factors is markedly diminished in the absence of the IFN-alpha/beta signalling complex
Yokota et al., J Rheumatol 2001
(Arthritis, Rheumatoid...) :
STAT1 and STAT3 are differentially regulated in
response to
IL-6 in different cell types
Terstegen et al., J Immunol 2001
:
We show in this study that infection of HeLa cells with VSV leads to a strongly diminished
activation of STAT3 and
STAT1 by the inflammatory cytokine
IL-6
Tanuma et al., Blood 2001
:
In addition, the study shows PTPepsilonC-DA enhances
activation of
STAT1 by
IL-6 as well
Ling et al., Crit Care Med 2002
:
In endotoxin treated rats, there was significant inhibition of
interleukin-6 activation of janus kinase-1, gp 130, the interleukin-6 receptor,
STAT1 , and STAT3
Majka et al., Exp Hematol 2002
(MAP Kinase Signaling System) :
We also observed that while TPO efficiently activated various signaling pathways in CD34+ cells, megakaryocytes, and platelets ( MAPK p42/44, PI-3K-AKT, STAT proteins ),
IL-6 stimulated phosphorylation of
STAT-1 , -3, and -5 proteins only in CD34+ cells and megakaryoblasts
Legendre et al., J Biol Chem 2003
:
In the present study, we show for the first time that
interleukin-6 (IL) , in the presence of its soluble receptor ( sIL-6R ),
induces activation of JAK1, JAK2, and
STAT1/STAT3 proteins in bovine articular chondrocytes
Chen et al., J Immunol 2003
:
15dPGJ ( 2 ) also attenuated
IL-6 induced tyrosine phosphorylation of
STAT1 and STAT3 in Hep3B hepatoma cells
Walia et al., FASEB J 2003
:
We show that pretreatment of cells with TGF-beta1 is associated with a down-regulation of
IL-6 induced tyrosine phosphorylation of
STAT1 and STAT3 and suppression of ICAM-1 expression
Zhang et al., Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2003
:
Comparison of
IL-6 induced
STAT1 activation in different responsive cells ... On the other hand,
IL-6 activated
STAT1 in a dose and time dependent manner in M1, R2 and U937 cells which underwent growth arrest and macrophage differentiation upon IL-6 induction ... These results suggest that
IL-6 induced
STAT1 activation might be associated with growth-inhibitory effects, and our data might help to explain why IL-6 exerts distinct biological effects in different target cells
Yuan et al., Carcinogenesis 2004
(Colorectal Neoplasms) :
IL-6 induced prominent tyrosine phosphorylation of the transcription factor
STAT1 in both cell types ... Following treatment with butyrate, the activation of
STAT1 in
response to
IL-6 , but not interferon-gamma, was completely lost ... Introduction of a soluble form of the IL-6Ralpha chain restored
IL-6 induced
STAT1 activation and resistance to apoptosis of butyrate treated cells
Usui et al., Hematol J 2004
(Multiple Myeloma) :
Upregulated production of
IL-6 , but not IL-10, by interferon-alpha induces SOCS3 expression and
attenuates STAT1 phosphorylation in myeloma cells
Cheon et al., J Immunol 2006
:
In contrast, PGE ( 2 ) suppressed
IL-6 induced phosphorylation of STAT3 and
STAT1
Chaudhuri et al., Blood 2008
(HIV Infections...) :
The
STAT1 inhibitor, fludarabine,
blocked HIV-1 induced
IL-6 , diminished HIV-1 induced claudin-5 and ZO-1 down-regulation, and blocked HIV-1- and IL-6 induced monocyte migration across a BBB model
Sanz et al., Glia 2008
:
Minimal
role for
STAT1 in
interleukin-6 signaling and actions in the murine brain ... The binding of
IL-6 to its receptor (IL6R) triggers gp130 mediated activation of
STAT1 and STAT3 as well as SHP2 phosphatase and ERK1/2 ... In conclusion, although
IL-6 can
activate STAT1 this plays minimal, if any, role in IL-6 signaling and actions in the CNS
Norkina et al., Alcohol Clin Exp Res 2008
:
Indeed, we observed significant down-regulation of IL-6-, IFNalpha- and IFNgamma induced
STAT1 DNA binding as well as
inhibition of
IL-6- and IFNgamma induced STAT3 when alcohol was added to monocytes 3 hours prior to the cytokine stimulation
Yang et al., Microvasc Res 2009
(AIDS Dementia Complex) :
Here, we report that HIV-1 gp120 protein activated
STAT1 and
induced interleukin (IL)-6 and IL-8 secretion in HBMEC ... The
STAT1 inhibitor, fludarabine,
prevented gp120 induced
IL-6 and IL-8 secretion ... Inhibitors of
STAT1 , mitogen activated protein kinase kinase ( MEK ) ( PD98059 ), and phosphatidyl inositol 3 kinase (PI3K) ( LY294002 ), blocked gp120 induced STAT1 activation and significantly
diminished IL-8-,
IL-6- , and gp120 induced monocyte adhesion and migration across in vitro BBB models
Efimova et al., Int J Radiat Biol 2009
(Neoplasms) :
Using Stat1 knock-downs we demonstrated that
IL6 and IL8 production is
Stat1 dependent ... This resistance to apoptosis is associated with
Stat1 dependent production of
IL6 and IL8 and suppression of caspases 8, 9 and 3
Bauer et al., Oncogene 2009
(Multiple Myeloma) :
However,
Stat1 activation in
response to
IL-6 or interferon-gamma was not affected by Cyp silencing or CsA treatment
Lee et al., Mol Cell 2009
(Inflammation) :
LXR ligands inhibit neither STAT1 phosphorylation nor
STAT1 translocation to the nucleus but, rather,
inhibit STAT1 binding to promoters and the expression of IRF1, TNFalpha, and
IL-6 , downstream effectors of STAT1 action
Valmas et al., PLoS Pathog 2010
(Hemorrhagic Fever, Ebola...) :
Consistent with this model, MARV infection and MARV VP40 expression also inhibit the Jak1
dependent ,
IL-6 induced tyrosine phosphorylation of
STAT1 and STAT3
Oiva et al., Crit Care 2010
(Acute Disease...) :
Also,
IL-6 induced
STAT1 phosphorylation was impaired while IL-4 induced STAT6 phosphorylation was enhanced
Lin et al., Int J Cancer 2012
(Multiple Myeloma) :
LLL12 also inhibited STAT3 phosphorylation
induced by
interleukin-6 (IL-6) and interferon-a but not
STAT1 , STAT2, STAT4 and STAT6 phosphorylation induced by interferon-a, interferon-? and IL-4 indicating the selectivity of LLL12 for STAT3
Riebe et al., Anticancer Res 2011
(Carcinoma, Squamous Cell...) :
Analyzing the effect of silencing of ERK1/2 MAPK revealed that this MAPK strongly influences
IL-6 and IL-8 expression, but is not
involved in either activation of
STAT1 or STAT3
Rosengren et al., Ann Rheum Dis 2012
(Arthritis, Rheumatoid) :
Interleukin-6 induced phosphorylation of
STAT1 and STAT3 was inhibited by CP-690,550 with IC ( 50 ) values of 23 and 77 nM, respectively
Tormo et al., Cytokine 2012
:
We analyzed
IL-6 induced
STAT1 , 3 and 5 activation by flow cytometry ( phosflow ) in mouse mononuclear cells and its effect on the level of the mRNA coding for cytokine-inducible SH2 containing protein ( CIS )
Wang et al., J Mol Med (Berl) 2013
:
These effects, in turn, may be mediated by EGCG induced downregulation of transducers
p-STAT1 and p-STAT4 for Th1, and p-STAT3 for Th17. EGCG induced change in Th17/Treg balance may be
mediated by its inhibition of
IL-6 signaling because EGCG inhibited soluble IL-6R, membrane gp130, and IL-6 induced phosphorylation of STAT3
Fahmi et al., Cell Signal 2013
(Hypertrophy...) :
In the absence of sIL-6R, IL-6 did not induce STAT1/3 phosphorylation, whereas
IL-6/sIL-6R and LIF
induced STAT1 and STAT3 phosphorylation
Oguro et al., Eur J Cancer 2013
(Carcinoma, Renal Cell...) :
In contrast, the
IL-6 inhibited
STAT1 phosphorylation, enhanced STAT3 phosphorylation and accelerated cell proliferation in ACHN cells
Qi et al., BMC bioinformatics 2013
:
In particular, the unbalanced competition between
STAT1 and STAT3 for IFNR and gp130
led to preferential activation of IFN-gamma and
IL-6 , while at the same time the formation of STAT1/3 heterodimers enhanced preferential signal transduction by sequestering a fraction of the activated STATs
Choi et al., J Immunol 2013
:
IL-6R signaling
activates the transcription factor
STAT1 specifically in CD4 T cells
Uzel et al., J Allergy Clin Immunol 2013
(Genetic Diseases, X-Linked...) :
STAT1 phosphorylation in
response to IFN-?,
IL-6 , and IL-21 was increased and prolonged
Wu et al., J Biol Chem 1996
:
However, only the latter is effective in native PC12 cells as the
activation of Stat3 and
Stat1 in native PC12 cells by
IL-6 fails to induce neuronal differentiation
Hemmann et al., J Biol Chem 1996
:
One example is the differential
activation of acute phase response factor ( APRF, also called Stat3 ) and
Stat1 by
interleukin 6 and interferon-gamma
Schaper et al., FEBS Lett 1997
(Carcinoma, Hepatocellular) :
These observations are in contrast to the rapid and transient activation of
STAT1 and STAT3
mediated by
IL-6
Jenab et al., Endocrinology 1997
:
Using the tyrosine phosphorylation inhibitor, genistein, and electrophoretic mobility shift assay, we show that
IL-6 and IFN-gamma
induce nuclear factor STAT-3 and
STAT-1 DNA binding activity to the sis-inducible element of c-fos in a genistein dependent pathway
Ogata et al., J Immunol 1997
(Multiple Myeloma) :
IL-6 triggered phosphorylation of
STAT1 and/or STAT3 in MM cells independent of their proliferative response to IL-6
Chung et al., Science 1997
:
Although
Stat1 is also phosphorylated in
response to
IL-6 , PIAS3 did not interact with Stat1 or affect its DNA binding or transcriptional activity