◀ Back to IL6
EPHB2 — IL6
Text-mined interactions from Literome
Valledor et al., J Biol Chem 2000
:
Granulocyte/macrophage colony stimulating factor,
interleukin 3, and TPA, all of which induced macrophage proliferation, also
induced ERK activity, which was maximal at 5 min poststimulation
Tancredi et al., J Neurochem 2000
(Synaptic Transmission) :
Both
effects of
IL-6 on STAT3 and
MAPK/ERK activation were effectively counteracted by LavA treatment
Lee et al., J Immunol 2000
(MAP Kinase Signaling System) :
Studies using pharmacological inhibitors demonstrate that both p38 MAPK and
ERK1/2 are
involved in ICAM-1 induced
IL-6 expression, whereas only ERK1/2 is important for IL-1alpha and IL-1beta expression
Harcourt et al., Eur J Biochem 2001
(MAP Kinase Signaling System) :
Pharmacologic inhibition of either the
ERK or the p38 MAPK pathway, using U0126 and SB203580, respectively,
reduced interleukin-6 protein induction by at least 70 %, and combined inhibition of both pathways fully blocked interleukin-6 protein expression and reduced interleukin-6 mRNA induction by more than 80 %
Kuo et al., Oncogene 2001
:
In Hep3B cells, the JAK/STAT3,
ERK , and PI 3-K/Akt pathways were
activated by
IL-6 stimulation
Abe et al., Osaka City Med J 2001
:
Interestingly, no requirement of the Y759 mediated signals, including SHP-2 mediated Erk/MAP kinase pathway, coincided with the failure of SHP-2, Gab1/Gab2, and
Erk/MAP kinase
activation by
IL-6 in MH60 cells
Tokunou et al., Arterioscler Thromb Vasc Biol 2001
:
These results suggest that the CRE site and CREB play an important role in thrombin induced
IL-6 gene expression in VSMCs. Transactivation of EGF-R and activation of
ERK and p38 MAPK are
involved in this process
Ishikawa et al., Blood 2002
(Multiple Myeloma) :
In multiple myeloma, IL-6 only enhanced the proliferation of CD45+ tumor cells that harbored the IL-6 independent activation of src family kinases even though STAT3 and
ERK1/2 could be activated in
response to
IL-6 in both CD45+ and CD45 ( minus sign ) cells
Le Gouill et al., Leukemia 2002
(Multiple Myeloma) :
The phosphorylation of both STAT3 and
ERK1/2 induced by
IL-6 was totally blocked at 15 microM of R115777 and partially blocked when R115777 was used at 10 and 5 microM
Legendre et al., J Biol Chem 2003
:
JAK/STAT but not
ERK1/ERK2 pathway
mediates interleukin (IL)-6/soluble
IL-6R down-regulation of Type II collagen, aggrecan core, and link protein transcription in articular chondrocytes
Kawano et al., Int J Hematol 2002
(MAP Kinase Signaling System...) :
In both CD45- and CD45+ U-266 cells, STAT3 and
MAPK(ERK1/2) can be activated in
response to
IL-6 equally between them, but src family kinases such as Lyn, Fyn can be activated only in CD45+ U-266 cells
Sengul et al., American journal of physiology. Renal physiology 2003
:
Inhibitors of
ERK , JNK, and p38
reduced LC-induced
IL-6 and MCP-1 production
Maggi et al., J Biol Chem 2003
(Cardiovirus Infections...) :
ERK activation is
required for double stranded RNA- and virus induced
interleukin-1 expression by macrophages
MacGillivray et al., J Biol Chem 2003
(MAP Kinase Signaling System) :
The protein tyrosine phosphatase SHP-2 regulates
interleukin-1 induced
ERK activation in fibroblasts
Shi et al., Mol Cancer Ther 2003
(Multiple Myeloma) :
FTIs were also able to abrogate the IL-6 proliferative response of WT ras expressing MM cells, and this was associated with inhibition of
IL-6 induced activation of
ERK , AKT, and p70
Xie et al., J Immunol 2003
:
Furthermore, LPS up-regulated the secretion of IL-1beta,
IL-6 , IL-8, IL-10, and TNF-alpha ; reduced Ag presentation capacity ; and
inhibited phosphorylation of
ERK , but activated p38, leading to a reduced NF-kappaB activity in treated cells
Ruiz et al., J Biol Chem 2004
:
15-deoxy-delta12,14-prostaglandin J2-mediated
ERK signaling
inhibits gram negative bacteria induced RelA phosphorylation and
interleukin-6 gene expression in intestinal epithelial cells through modulation of protein phosphatase 2A activity
Chang et al., J Biol Chem 2004
(Inflammation...) :
The induction of prostaglandin E2 production,
interleukin-6 production, cell cycle arrest, and cytotoxicity in primary oral keratinocytes and KB cancer cells by areca nut ingredients is differentially
regulated by
MEK/ERK activation ... The induction of prostaglandin E2 production,
interleukin-6 production, cell cycle arrest, and cytotoxicity in primary oral keratinocytes and KB cancer cells by areca nut ingredients is differentially
regulated by
MEK/ERK activation
Wang et al., J Biol Chem 2005
:
SHP-2 modulates
interleukin-1 induced Ca2+ flux and
ERK activation via phosphorylation of phospholipase Cgamma1
Moran et al., Liver Int 2005
(Carcinoma, Hepatocellular...) :
Using in vitro cell cultures, we demonstrated that
IL-6 stimulated STAT3 and
extracellular regulated kinase (ERK) activity in both HCC cells and isolated hepatocytes ... However, while STAT3 activation profiles were similar,
IL-6 stimulated
ERK activity in a biphasic manner in HCC cells and a monophasic, sustained ERK activation in hepatocytes
Li et al., J Biol Chem 2005
(Arteriosclerosis...) :
However, MKK3/p38 signaling was specifically involved in TNF-alpha induction, and
Erk1/2 signaling was
required for
IL-6
Deura et al., Fertil Steril 2005
(Endometriosis...) :
IL-6 markedly
enhanced the phosphorylation of
ERK1/2 , but not Stat3 and p38 MAPK ... U0126 markedly reduced the level of the
IL-6 induced phosphorylation of
ERK1/2
Jeong et al., Hear Res 2005
(MAP Kinase Signaling System) :
Increased
IL-6 by DFX was significantly
inhibited by p38 inhibitor, SB203580 ( about 72 % inhibition, P=0.027 ) but not
ERK inhibitor, PD98059 or JNK inhibitor, SP600125
Legendre et al., J Rheumatol 2005
(MAP Kinase Signaling System) :
IL-6/sIL-6R markedly
induced activation of STAT and extracellular signal related kinase (
ERK1/2 ) and the subsequent expression of the collagenases MMP-1 and MMP-13 as well as MMP-3, an aggrecan degrading enzyme and activator of pro-MMP
Wang et al., Cell Signal 2005
(MAP Kinase Signaling System...) :
Differential activation of the MEK/ERK and PI3K/AKT pathways that result in differential secretion IL-6, IL-8, TIMP-2 and VEGF were seen contingent on the cell type examined ; VEGF and TIMP-2 expression in PC3 cells are dependent on AKT activation and
ERK activation in LNCaP and LNCaP C4-2B cells
leads to
IL-6 or IL-8 secretion
Miranda et al., Leuk Res 2005
(MAP Kinase Signaling System) :
Additionally,
interleukin-3 , which inhibits G-CSF induced differentiation of 32 Dc l3 cells, also
inhibited the ability of G-CSF to stimulate prolonged
MEK/ERK activation
Ganesan et al., Blood 2006
(Inflammation) :
Inhibition of
Ras/Erk or PI3K
suppressed the enhanced production of
IL-6 in SHIP-deficient macrophages
Thobe et al., Am J Physiol Cell Physiol 2006
(Anoxia...) :
Furthermore, administration of PP1 prevented the hypoxia induced increase in IL-6 but not MCP-1 release by KC. Additional in vitro results suggest that p38 but not
ERK1/2 or JNK are
critical for KC
IL-6 production
Aoki et al., J Cell Biochem 2006
:
In addition,
IL-6 activated
ERK in PSCs
Hayer et al., Arthritis Rheum 2007
(Arthritis...) :
Early lesions were associated with up-regulation of interleukin-1 (IL-1) and
IL-6 as well as
activation of p38 MAPK and
ERK
Kwon et al., J Dermatol Sci 2007
(MAP Kinase Signaling System) :
These results suggest that SPC induced
IL-6 production is
mediated by PKC dependent p42/44
ERK activation in human dermal fibroblasts cultured in vitro
Gazi et al., Clin Chim Acta 2007
(Prostatic Neoplasms) :
Interestingly, although sodium selenite did not show effect on activation of both STAT3 and
ERK1/2 in the
presence of
IL-6 , an increased expression of c-Jun was detected in cells after treatment with sodium selenite
Kobayashi et al., Eur J Pharmacol 2007
:
These results suggest that
ERK and calcineurin are cooperatively
involved in UTP induced
IL-6 production
Sanz et al., Glia 2008
:
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
Yang et al., Cell Signal 2008
(MAP Kinase Signaling System) :
IL-1beta stimulated activation of
ERK1/2 and p38alpha MAPK
mediates the transcriptional up-regulation of
IL-6 , IL-8 and GRO-alpha in HeLa cells
Krady et al., J Neurosci Res 2008
:
IL-6 markedly
increases STAT-3 and
ERK phosphorylation after 20 min of treatment, whereas these signal transducers are weakly stimulated by CNTF across a range of doses
Venkatachalam et al., Am J Physiol Heart Circ Physiol 2008
(Hyperglycemia) :
Resveratrol inhibits high glucose induced
PI3K/Akt/ERK dependent
interleukin-17 expression in primary mouse cardiac fibroblasts
Sobota et al., Cell Signal 2008
:
Mouse embryonic fibroblasts expressing a SIRP1alpha protein which lacks the intracellular part show enhanced SHP2 phosphorylation and
ERK1/2 activation in
response to
IL-6 , suggesting that SIRP1alpha affects IL-6 signalling through SHP2
Kang et al., Cell Prolif 2008
(MAP Kinase Signaling System) :
Interestingly, IL-6 activated MAPKs but EGF did not influence JAK2/STAT3 activation ; AG490 specifically inhibited
IL-6 induced
Erk1/2 phosphorylation without affecting IL-6 induced phosphorylation of Raf and MEK1/2
Kogut et al., Innate Immun 2008
:
Flagellin and lipopolysaccharide up-regulation of
IL-6 and CXCLi2 gene expression in chicken heterophils is
mediated by
ERK1/2 dependent activation of AP-1 and NF-kappaB signaling pathways
Hashizume et al., Rheumatology (Oxford) 2008
(Arthritis, Rheumatoid) :
Finally,
IL-6/sIL-6R induced phosphorylation of STAT3 and
ERK1/2 in RA-FLS, and was completely inhibited by PAR and PD, respectively
Sommer et al., Vet Immunol Immunopathol 2009
:
In uninfected cells, inhibition of MAPK revealed that CD40L mediated increase in
IL-6 gene expression was
dependent on activation of
ERK1/2 , while increases in IL-12p40, iNOS, and IL-10 gene expression were dependent on activation of p38
Wang et al., Neurosci Lett 2009
:
IL-6 induced STAT3 phosphorylation was inhibited by AG490 but not by PD98059 ; and
IL-6 induced
ERK1/2 activation was blocked by PD98059 but not by AG490
Kirchmeyer et al., Arthritis Res Ther 2008
(MAP Kinase Signaling System) :
Among RAR and RXR agonists, only ATRA inhibited IL-1 induced IL-6 expression in rat synovial fibroblasts by inhibiting
ERK1/2 pathway and subsequent
activation of AP-1 and
NF-IL-6 independently of RAR
Huang et al., J Mol Endocrinol 2009
:
Urocortin
induces interleukin-6 release from rat cardiomyocytes through p38 MAP kinase,
ERK and NF-kappaB activation ... Finally, the CRH-R antagonists alpha-helical ( 9-41 ) CRH and astressin-2B completely inhibit Ucn induced
IL-6 release, as well as
activation of
ERK , p38, and NF-kappaB
Chan et al., J Pharmacol Exp Ther 2009
(Pancreatitis) :
cAMP-responsive element binding protein ( CREB ) might be involved in
ERK1/2 induced
IL-6 expression because phosphorylation of CREB was observed after angiotensin II treatment, which was reversed by losartan and the ERK1/2 inhibitor
Lin et al., Journal of neuroinflammation 2009
:
Whereas
IL-6 activated STAT-3 and
ERK phosphorylation, CNTF did not activate these pathways, nor did CNTF increase p38 MAP kinase phosphorylation
Wang et al., FASEB J 2009
(MAP Kinase Signaling System) :
In the present study, we demonstrate that CGRP is involved in morphine tolerance by differentially regulating the
ERK dependent up-regulation of IL-1beta, TNF-alpha, and microsomal prostaglandin E synthase-1 ( mPGES-1 ) in astrocytes and p38 dependent up-regulation of
IL-6 in microglia in the rat spinal cord
Park et al., Mol Oncol 2008
(Multiple Myeloma) :
Upon treatment with curcumin,
IL-6/sIL-6R induced STAT3 and
Erk phosphorylation was dramatically reduced in the co-cultured cells ... In a combination treatment with curcumin and bortezomib,
IL-6/sIL-6R induced STAT3 and
Erk phosphorylation was effectively inhibited
Filer et al., Arthritis Rheum 2009
(Arthritis, Rheumatoid) :
The MAPKs p38, JNK, and
ERK were
necessary for
IL-6 production, but phosphatidylinositol 3-kinase ( PI 3-kinase ) was required for selective CCL5 induction
Woolson et al., Cell Signal 2009
:
Here we demonstrate that elevation of cyclic AMP ( cAMP ) levels in human umbilical vein endothelial cells ( HUVECs ) specifically attenuates
ERK1,2 activation in
response to either leptin or a soluble
interleukin IL-6 receptor-alpha/IL-6 ( sIL-6R alpha/IL-6 ) trans signalling complex but not protein kinase C activator phorbol 12-myristate 13-acetate ... The inhibitory effects of cAMP on sIL-6R
alpha/IL-6 stimulated phosphorylation of
ERK1,2 and STAT3 were abolished by either short interfering ( si ) RNA mediated knockdown or genetic ablation of suppressor of cytokine signalling-3 ( SOCS-3 ) ... Interestingly, the ability of cAMP elevation to inhibit
IL-6 signalling was
blocked by
ERK inhibition
Saraiva et al., Immunity 2009
:
Interleukin-10 production by Th1 cells requires
interleukin-12 induced STAT4 transcription factor and
ERK MAP kinase activation by high antigen dose
Cuong et al., Life Sci 2009
(Inflammation...) :
Pre-treatment with C-K significantly inhibited zymosan mediated secretion of tumor necrosis factor-alpha,
interleukin (IL)-6 , and IL-12 p40, and the
activation of
ERK1/2 and p38 ... Pre-treatment with C-K significantly inhibited zymosan mediated secretion of tumor necrosis factor-alpha,
interleukin (IL)-6 , and IL-12 p40, and the
activation of
ERK1/2 and p38
Totlandsdal et al., Toxicol In Vitro 2010
:
Cellular release of IL-1alpha, IL-1beta and
IL-6 was significantly
attenuated by curcumin and by inhibitors of the MAPKs
ERK1/2 ( PD98069 ), p38 ( SB202190 ) and JNK ( SP600125 ), whereas pyrrolidine dithiocarbamate ( PDTC ) attenuated the release of IL-6, but not of IL-1alpha and IL-1beta
Iqbal et al., Biochem Biophys Res Commun 2010
(Multiple Myeloma) :
The
IL-6 induced phosphorylation of STAT3 and
ERK1/2 was not up-regulated in the Lyn overexpressed cells, indicating that the Lyn-PI 3-kinase-Akt pathway is independent of these pathways
Nomi et al., Invest Ophthalmol Vis Sci 2010
:
The zymosan induced release of
IL-6 and IL-8 was
attenuated by inhibitors of
ERK , p38, JNK, and NF-kappaB signaling
Zha et al., PloS one 2010
:
Berberine significantly
inhibited HIV PI-induced TNF-alpha and
IL-6 expression by modulating ER stress signaling pathways and subsequent
ERK activation, in turn preventing the accumulation of the RNA binding protein HuR in cytosol and inhibiting the binding of HuR to the 3'-UTRs of TNF-alpha and IL-6 in macrophages
Huang et al., Mediators Inflamm 2009
(MAP Kinase Signaling System) :
Upregulation of Salmonella induced
IL-6 production in Caco-2 cells by PJ-34, PARP-1 inhibitor : involvement of PI3K, p38 MAPK,
ERK , JNK, and NF-kappaB
Xuan et al., Cell Physiol Biochem 2010
:
Both LPS and GA stimulated the production of
IL-6 , IL-10, IL12p70 and TNFalpha in a p38- and/or
ERK dependent manner
Chen et al., Biochem Biophys Res Commun 2010
(Bone Resorption...) :
ERK1/2 is
involved in cyclic compressive force induced
IL-6 secretion in MLO-Y4 cells
Fan et al., J Cell Physiol 2011
:
Inhibitors of AMPK ( araA ), p38MAPK ( SB202190 ), and
ERK1/2 ( PD98059 and U0126 ) but not JNK ( SP600125 )
suppressed gAd induced
IL-6 production
Lo et al., Cancer Res 2011
(Ascites...) :
ERK activation by the
IL-6/sIL-6Ra complex increased endothelial integrity via Src kinase activation and Y685 phosphorylation of VE-cadherin
Wang et al., Inflamm Res 2011
:
TNF-a induced phosphorylation of ERK1/2 and JNK, and TNF-a induced
IL-6 expression and release were
inhibited by selective
ERK1/2 and JNK blockers
Vitiello et al., Microbiol Immunol 2011
:
Using two potent and selective inhibitors of MEK activation by Raf-1 ( PD-098059 ) and p38 ( SB-203580 ), it was also demonstrated that both
ERK1/2 and p38 pathways
play key roles in the production of
IL-6 as well as in ICAM-1, VCAM-1 and E-selectin expression by Hib porin
Kim et al., Immune network 2011
:
We further demonstrated that JNK activation was required for TAT-CD137Lct induced production of TNF-a, while activation of
Erk and p38 MAPK were
involved in
IL-6 and TNF-a production
Luckett-Chastain et al., J Interferon Cytokine Res 2012
:
Inhibition of STAT3 in fibroblasts potentiated
IL-6R induced
ERK phosphorylation and vice versa
Chao et al., Connect Tissue Res 2012
(Hypertrophy...) :
It was also found that NF-?B inhibitor, but not
ERK1/2 inhibitor,
attenuated EDP dependent induction of IL-1a, IL-1ß, and
IL-6 expression, indicating that NF-?B pathways are required for EDP induced IL-1a, IL-1ß, and IL-6 gene expression in human LF cells
Chen et al., J Mol Med (Berl) 2012
(Multiple Myeloma) :
Further analysis demonstrated that ISL not only downregulated IL-6 expression but also significantly decreased levels of phosphorylated ERK and STAT3 and could inhibit phosphorylation levels of
ERK and STAT3
induced by recombinant human
IL-6 , which are critical signaling proteins in IL-6 signaling regulation networks
Maza et al., Microbes Infect 2012
:
Moreover, P. brasiliensis yeasts induced activation of p38 mitogen activated protein kinase ( MAPK ), c-Jun NH ( 2 ) -terminal kinase ( JNK ) and extracellular signal regulated kinase ( ERK ) 1/2 in A549 cells, and IL-8 and
IL-6 secretion promoted by this fungus was
dependent on activation of p38 MAPK and
ERK 1/2
Kim et al., Parasite Immunol 2013
:
N. fowleri
mediated IL-1ß and
IL-6 expression requires
ERK , JNK and p38 mitogen activated protein kinases ( MAPKs ) activation in astrocytes
Nasimian et al., Inflamm Res 2013
:
NF-kB, JNK, p38 and
ERK specific inhibitors significantly
reduced the production of TNF-a and
IL-6 in macrophages stimulated with palmitate and also PTP1B knockdown cells
Fahmi et al., Cell Signal 2013
(Hypertrophy...) :
In conclusion, IL-6 can signal in cardiomyocytes independent of sIL-6R and STAT1/3 and furthermore, that
Erk1/2 and PI3K
activation by
IL-6 are both necessary and sufficient for induced cardioprotection
Wang et al., Mol Cell Biochem 2013
:
By western blot analysis, DHA and EPA inhibited
IL-6 induced STAT3 phosphorylation but not
ERK1/2 or C/EBPß
Geletu et al., Biochim Biophys Acta 2013
(MAP Kinase Signaling System) :
Further examination indicated that, although IL6 was able to activate Erk in sparsely growing cells,
IL6 could not induce an
increase in
Erk activity levels in densely growing cultures ... Most importantly, cadherin-11 knock-down did allow
Erk activation by
IL6 at high densities, indicating that it is indeed cadherin engagement that prevents Erk activation by IL6
Lee et al., Food Chem Toxicol 2013
:
Further studies revealed that PL suppressed the production of tumor necrosis factor-a (TNF-a) or
Interleukin (IL)-6 and
activation of nuclear factor-?B ( NF-?B ) or
extracellular regulated kinases (ERK) 1/2 by LPS
Li et al., Mol Cell Biochem 2013
(MAP Kinase Signaling System) :
IL-6 also
induces a temporary and significant activation of
ERK , but not sustained activation, and change sustained activation in MPP ( + ) -treated group into temporary activation
Wei et al., Spine (Phila Pa 1976) 2013
:
IL-1 induced nitric oxide, prostaglandin E-2, and
IL-6 accumulation were also
reduced by
ERK inhibition
Tsai et al., PloS one 2013
:
Bla g 2 can stimulate up-regulation of inflammatory cytokines including TNF-alpha and
IL-6 and
activation of nuclear factor kappa B ( NF-kB/p65 ), p38 mitogen activated protein kinase ( p38 ),
ERK , and JNK in cultured fibrocytes ... This increased secretion of TNF-alpha and
IL-6 and
activation of NF-kB,
ERK , and JNK was significantly inhibited by the addition of either mannan or mannose
Wu et al., J Biol Chem 1996
:
Mechanistically, NGF and bFGF
induce a sustained phosphorylation and activation of
ERK1 and ERK2 in both cells, while
IL-6 produces only a transient and weak tyrosine phosphorylation
Wu et al., J Biol Chem 1996
:
Importantly,
IL-6 does not
enhance ERK phosphorylation in the presence of either NGF or EGF
Geng et al., J Clin Invest 1996
:
However,
ERK was also
activated by PDGF, IGF-1, and
IL-6
Berger et al., Blood 1997
(Multiple Myeloma) :
Prior treatment of U266 cells with IFN-beta downregulated
IL-6 induced tyrosine phosphorylation of gp130, Jak2, PTP1D/Syp, Shc, and
Erk2 , and GTP loading of p21ras
Lo et al., J Biol Chem 1998
:
Requirements of focal adhesions and calcium fluxes for
interleukin-1 induced
ERK kinase activation and c-fos expression in fibroblasts