◀ Back to TLR4
IRF3 — TLR4
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
IRF3
→
TLR4
(increases, TLR4 Activity, IRF3 Activity)
Cusson-Hermance et al., J Biol Chem 2005
Evidence: In addition to activating NF-kappaB, TLR3/4 pathways also stimulate interferon regulatory factor 3 activation.
-
Reactome Reaction:
IRF3
→
TLR4
(reaction)
Fitzgerald et al., Nat Immunol 2003, Fitzgerald et al., J Exp Med 2003, Mori et al., J Biol Chem 2004, Hemmi et al., J Exp Med 2004, An et al., Immunity 2006, Panne et al., J Biol Chem 2007, Lin et al., Mol Cell Biol 1998
-
Reactome Reaction:
IRF3
→
TLR4
(indirect_complex)
Fitzgerald et al., J Exp Med 2003, Mori et al., J Biol Chem 2004, Hemmi et al., J Exp Med 2004, An et al., Immunity 2006, Lin et al., Mol Cell Biol 1998
Text-mined interactions from Literome
Sakaguchi et al., Biochem Biophys Res Commun 2003
:
Although much has been studied about the activation of the transcription factor
IRF-3 and
induction of IFN-beta gene by the LPS mediated
TLR4 signaling, definitive evidence is missing about the actual role of IRF-3 in LPS responses in vitro and in vivo
Takahasi et al., Nat Struct Biol 2003
:
Transcription factor
IRF-3 is post-translationally
activated by
Toll-like receptor ( TLR ) signaling and has critical roles in the regulation of innate immunity
Wietek et al., J Biol Chem 2003
:
Interferon regulatory factor-3 mediated
activation of the interferon-sensitive response element by
Toll-like receptor (TLR) 4 but not TLR3 requires the p65 subunit of NF-kappa ... These results therefore indicate that
IRF-3 mediated
activation of the ISRE by
TLR4 but not TLR3 requires the p65 subunit of NF-kappa B
Okamoto et al., Clin Diagn Lab Immunol 2004
(Neoplasms, Experimental) :
Cytokine production, killer cell activities, maturation of dendritic cells, phosphorylation of mitogen activated protein kinases, and nuclear translocation of
interferon-regulatory factor 3 induced by AILb-A were severely
impaired in
TLR4-deficient but not TLR2-deficient mice
Goriely et al., Blood 2006
:
Interferon regulatory factor 3 is
involved in
Toll-like receptor 4 (TLR4)- and TLR3 induced IL-12p35 gene activation
Cheng et al., J Immunol 2006
:
IRF-3 is expressed ubiquitously and is
activated by serine phosphorylation in response to viral infection or
TLR signaling
Lundberg et al., Blood 2007
(Inflammation) :
Furthermore,
TLR3 stimulation did not
activate NFkappaB, MAPKs, or
IRF-3 in DCs and MOs, but was able to do so in ECs and RA-SF
Koziczak-Holbro et al., Eur J Immunol 2008
:
TLR4 mediated
IRF3 activation was intact in these cells
Abe et al., Arterioscler Thromb Vasc Biol 2008
(Inflammation...) :
Statins inhibited
TLR4 mediated
activation of
interferon ( IFN ) regulatory factor ( IRF)3 by either lipopolysaccharide (LPS) or palmitic acid, resulting in suppression of IFN-beta expression, but not that of NF-kappaB or JNK
McCoy et al., J Biol Chem 2008
:
Glucocorticoids inhibit
IRF3 phosphorylation in
response to
Toll-like receptor-3 and -4 by targeting TBK1 activation ...
IRF3 can be
activated by Toll-like receptor 3 (TLR3) in response to the double stranded RNA mimic poly ( I-C ) and by
TLR4 in response to lipopolysaccharide (LPS)
Xu et al., Mol Immunol 2008
:
PTP1B inhibits
TLR ligands induced
activation of MAPKs, NF-kappaB, and
IRF3 , furthermore, co-transfection of PTP1B inhibits both MyD88- and TRIF induced transcription of TNF-alpha and IFN-beta reporter genes in a dose dependent manner
Youn et al., Int Immunopharmacol 2009
:
Guggulsterone suppresses the activation of transcription factor
IRF3 induced by TLR3 or
TLR4 agonists
Knödler et al., Leukemia 2009
:
IL-10 was found to downregulate MyD88, IRAK1 ( IL-1 receptor associated kinase ) and tumor necrosis factor receptor associated factor 6, essential adaptor molecules for TLR signaling, and to decrease
TLR induced nuclear expression of the nuclear factor-kappaB transcription factors c-Rel and Rel-B as well as
interferon regulatory factor (IRF)-3 and IRF-8
Seya et al., Immunol Rev 2009
(RNA Virus Infections) :
In response to RNA stimulation,
TLR3 recruits the Toll-interleukin 1 receptor domain ( TIR ) -containing adapter molecule 1 ( TICAM-1 ) adapter and
induces IRF-3 activation followed by IFN-beta promoter activation
Wu et al., Hepatology 2009
:
TLR stimulated expression of proinflammatory cytokines [ tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) ], and activation of
IRF-3 was suppressed after up-regulation of HBV replication in HBV-Met cells
Lee et al., Biochem Pharmacol 2009
:
Luteolin attenuated ligand independent activation of
IRF3 or NFkappaB
induced by
TLR4 , TRIF, or TBK1, while it did not inhibit TLR oligomerization
Atzei et al., J Biol Chem 2010
:
We now describe the first functional characterization of the human ortholog of Cactin ( hCactin ) and show that it acts as a negative regulator of TLRs. Overexpression of hCactin suppresses
TLR induced
activation of NF-?B and
interferon-regulatory factor transcription factors and induction of TLR-responsive genes, whereas knockdown of endogenous hCactin augments TLR induction of these responses
Chiang et al., J Biol Chem 2012
(Calcium Signaling) :
Previous work has demonstrated that
TLR4 initiates NF-?B activation from the plasma membrane, but that subsequent TLR4 translocation to the endosomes is
required for
IRF3 activation ... In conclusion, our results describe a novel role of the PLC?2-IP ( 3 ) -Ca ( 2+ ) cascade in the LPS induced innate immune response pathway where release of intracellular Ca ( 2+ ) mediates
TLR4 trafficking and subsequent
activation of
IRF3
Tong et al., Cell Res 2012
:
NLRC5 ablation reduces MHC class I expression, and enhances IKK and
IRF3 phosphorylation in
response to
TLR stimulation or viral infection
Dowling et al., J Nutr Biochem 2013
:
Furthermore the c9,t11-CLA isomer inhibited both nuclear factor-?B ( NF-?B ) and
IRF3 activation following
TLR4 ligation while eicosapentaenoic acid ( EPA ) only suppressed NF-?B activation
Bagchi et al., Cytokine 2013
:
TLR4 activation
led to the translocation of the
interferon regulatory factor 3 (IRF3) into the nucleus
Chattopadhyay et al., mBio 2013
(Bacterial Infections...) :
The critical transcription factor for IFN induction, in both cases, is
IRF-3 , which is
activated by TLR3 or RIG-I signaling in response to virus infection and
TLR4 signaling in response to bacterial infection
Zhong et al., Science signaling 2013
(MAP Kinase Signaling System...) :
Deficiency in USP25 enhanced the extent of ubiquitination of TRAF3 and accelerated its degradation after TLR4 activation, which potentiated
TLR4 induced activation of NF-?B ( nuclear factor ?B ) and MAPK ( mitogen activated protein kinase ) signaling, but
inhibited activation of the transcription factor
IRF3 ( interferon regulatory factor 3 )