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TLR4 — TNF
Pathways - manually collected, often from reviews:
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TNF
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TLR4
(increases, TNF Activity)
Evidence: In Tlr4(WT) mice, subacute and chronic CS exposure induced a substantial pulmonary infiltration of macrophages, neutrophils, lymphocytes and dendritic cells (DCs), that was absent in air-exposed mice. n contrast, after subacute CS exposure, Tlr4(defective) mice showed a limited (5-fold lower) increase of DCs, neutrophils and lymphocytes in BAL fluid, lower costimulatory marker expression on DCs and lower MCP-1 and TNF-alpha levels in BAL fluid compared to Tlr4(WT) animals.
Text-mined interactions from Literome
Means et al., J Immunol 2001
(Tuberculosis) :
Together, these data suggest that Mtb induced
TNF-alpha production is largely
dependent on
TLR signaling
Tsan et al., Am J Physiol Cell Physiol 2001
:
These data demonstrate that, like
TNF-alpha , induction of MnSOD by LPS is
mediated by mCD14 and
TLR4 in murine macrophages
Supajatura et al., J Immunol 2001
(Acute Disease...) :
Using BMMCs from the genetically TLR4 mutated strain C3H/HeJ, we demonstrated that functional
TLR4 was
required for a full responsiveness of BMMCs to produce inflammatory cytokines ( IL-1beta,
TNF-alpha , IL-6, and IL-13 ) by LPS stimulation
McCurdy et al., J Leukoc Biol 2001
:
Using these models, we demonstrated that the BMMC IL-6 and
TNF-alpha responses to LPS were completely
dependent on functional
TLR4 with no significant LPS response observed in its absence
Li et al., Cell Growth Differ 2002
:
Furthermore, up-regulation of TLR2 and CD14 mRNA expression by PMA was abrogated by a protein kinase C inhibitor, Calphostine C, suggesting the up-regulation of TLR2 and CD14 mRNA is dependent on the activation of protein kinase C. Coexpression of CD14/TLR2 and/or
CD14/TLR4 may be
essential but not sufficient for the production of
tumor necrosis factor-alpha in response to lipopolysaccharide in our system
Abreu et al., J Biol Chem 2002
:
IFN-gamma regulates MD-2 expression in both IEC lines, whereas IFN-gamma and
TNF-alpha regulate
TLR4 mRNA expression in IEC lines
Netea et al., J Infect Dis 2002
(Candidiasis) :
Production of
tumor necrosis factor (TNF) and interleukin (IL)-1alpha and IL-1beta by mouse macrophages in response to C. albicans stimulation was not
affected by
TLR4 , and the candidacidal capacities of the neutrophils and macrophages of C3H/HeJ mice were normal
Iwadou et al., J Int Med Res 2002
(Gram-Negative Bacterial Infections...) :
The results suggest that gabexate mesilate induced inhibition of
tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18) production in LPS stimulated PBMCs is
due to the inhibition of the nuclear factor-kappa B activation pathway and/or inhibition of the processing pathway of pro-TNF-alpha and pro-IL-18, not to down-regulation of TLR-2 or
TLR-4
Takami et al., J Immunol 2002
:
Moreover, various
TLR ligands ( e.g., peptidoglycan, poly ( I:C ) dsRNA, LPS, and CpG motif of unmethylated DNA, which act as ligands for TLR2, 3, 4, and 9, respectively )
induced NF-kappa B activation and up-regulated
TNF-alpha production in osteoclast precursor cells
Royle et al., J Immunol 2003
:
In conclusion, we show for the first time that production of NO and
TNF-alpha is critically
dependent on activation of
TLR-4 by LPS during invasion of macrophages by salmonellae, but that different patterns of activation of intracellular signaling pathways are induced by purified LPS vs live salmonellae
Tamandl et al., Shock 2003
(Inflammation...) :
Here, we evaluated
TLR-4 expression of isolated monocytes in the
presence of
tumor necrosis factor (TNF)-alpha , interleukin (IL) 6, IL-8, and IL-10, and we investigated cellular activation of this treatment ...
TNF-alpha significantly
down-regulated TLR-4 mRNA expression after 6 h ( 100 % vs. 38.5 % +/- 4 % ; P < 0.05 )
Lucas et al., J Immunol 2003
:
TLR ligands
induced early and sustained secretion of
TNF-alpha , macrophage-inflammatory protein (MIP) 1alpha and MIP-2 with later secretion of IL-10, IL-12, and TGF-beta1 ; apoptotic cells alone stimulated late TGF-beta1 secretion only
Brito et al., Exp Eye Res 2004
:
Incubation of explants with a neutralizing anti-toll-like receptor-4 monoclonal antibody was used to determine if lipopolysaccharide stimulation of
tumor necrosis factor or interleukin-6 secretion was
dependent on
Toll-like receptor-4 activity
Mann et al., Infect Immun 2004
(Bordetella Infections...) :
However, early
tumor necrosis factor alpha (TNF-alpha) mRNA expression is primarily
dependent on
TLR4 and in vitro and in vivo protein levels substantiate this finding ... TLR4-deficient mice and TNF-alpha-/- mice are similarly susceptible to infection with relatively low doses of B. bronchiseptica and in vivo neutralization studies indicate that it is the
TLR4 dependent early elicited
TNF-alpha response that is critical for preventing severe pneumonia and limiting bacterial growth
Goral et al., J Immunol 2005
(Inflammation) :
Furthermore, different
TLR ligands
stimulated IL-6 and
TNF-alpha production via signaling pathways, which showed unique characteristics
Lorenz et al., Infect Immun 2005
(Acute Disease...) :
In response to H. influenzae htrB infection,
tumor necrosis factor alpha (TNF-alpha) secretion remained
TLR4 dependent
Chen et al., J Huazhong Univ Sci Technolog Med Sci 2004
:
Moreover, hsp70 induced
TNF-alpha production by human monocytes was
inhibited by
anti-TLR4
Zariffard et al., J Infect Dis 2005
(Vaginosis, Bacterial) :
Anti-TNF- alpha antibody blocked increases in TLR4 mRNA expression induced by CVL samples from women with BV, indicating that
TNF- alpha plays a critical role in induction of
TLR4
Maldonado-Bernal et al., Parasite Immunol 2005
:
The interaction of LPPG with TLR2 and
TLR4 resulted in activation of NF-kappaB and release of interleukin (IL)-10, IL-12p40,
tumour necrosis factor (TNF)-alpha , and IL-8 from human monocytes
Levy et al., J Endotoxin Res 2005
:
Differences between newborns and adults with respect to
TLR induced
TNF-alpha release extend to a range of TLR agonists, including bacterial lipopeptides, and are due to differences in soluble factors present in blood plasma ... Soluble factors in neonatal blood plasma suppress
TLR induced
TNF-alpha release from monocytes and efforts to identify and characterize these inhibitors are on-going
Suliman et al., FASEB J 2005
:
In wild-type ( Wt ) mice injected with heat inactivated E. coli, hepatic TLR4 and TLR2 proteins were up-regulated with
TLR dependent increases in transcript levels for
tumor necrosis factor ( TNF-alpha ), interleukin 6, nitric oxide synthase-II ( iNOS ), and NADPH oxidase 2 (Nox2)
Tachado et al., Am J Respir Cell Mol Biol 2005
(HIV Infections...) :
HIV impairs
TNF-alpha release in
response to
Toll-like receptor 4 stimulation in human macrophages in vitro ... Pharmacologic inhibition of endogenous cellular phosphatases increased ERK1/2 phosphorylation and partially restored
TLR4 mediated
TNF-alpha release in HIV+ macrophages
Clarke et al., J Am Coll Surg 2005
(Melanoma, Experimental) :
Stimulation of
Toll-like receptor 4 (TLR-4) activates macrophages and
results in the release of
TNF-alpha
Gutiérrez-Cañas et al., Rheumatology (Oxford) 2006
(Arthritis, Rheumatoid...) :
TLR4 and MyD88 mRNA and proteins were
induced by LPS and
TNF-alpha in RA FLS
Flandin et al., Eur J Immunol 2006
(Inflammation...) :
Silencing of TLR3, TLR2, IRAK-1 and myeloid differentiation factor 88 ( MyD88 ) expression by RNA interference revealed that both
TLR are
involved in the secretion of NO and
TNF-alpha induced by L. donovani promastigotes
Deering et al., Clinical and vaccine immunology : CVI 2006
:
Although a number of variables influence
TLR ligand
induced TNF responses, this assay can be optimized for potential clinical use to screen patients with primary immunodeficiencies affecting TLR function
Wang et al., Hepatobiliary Pancreat Dis Int 2006
(Disease Models, Animal...) :
TLR4 activation
causes partial hepatic I/R injury through release of
TNF-alpha
Horwood et al., J Immunol 2006
:
Bruton 's tyrosine kinase is required for TLR2 and
TLR4 induced
TNF , but not IL-6, production ... Furthermore, using the p38 inhibitor SB203580, we show that the
TLR4 induced production of
TNF , but not IL-6, requires the activity of p38 MAPK
Szczepański et al., Eur Arch Otorhinolaryngol 2006
(Cholesteatoma, Middle Ear...) :
TLR-ligand binding
results in cell signal transduction and subsequent production of various proinflammatory cytokines such as IL-1 and
TNF-alpha
Banus et al., Infect Immun 2006
(Genetic Predisposition to Disease...) :
Functional
Tlr4 is
essential for an efficient IL-1-beta,
TNF-alpha , and IFN-gamma response ; efficient clearance of bacteria from the lung ; and reduced lung pathology
Hu et al., Immunity 2006
(Arthritis...) :
We report that IFN-gamma augments
induction of
TNFalpha by
TLR ligands, immune complexes, and zymosan by suppressing IL-10 production and thereby interrupting Stat3 mediated feedback inhibition
Song et al., Biochem Biophys Res Commun 2006
(Insulin Resistance) :
In addition, activation of
TLR4 with either LPS or free fatty acids
stimulated NFkappaB signaling and expression of inflammatory cytokine genes, such as
TNFalpha and IL-6 in 3T3-L1 adipocytes
Paul-Clark et al., Br J Pharmacol 2006
:
6. These observations are the first to clearly delineate the
role of separately activating TLR2 and
TLR4 in the induction of NOSII and
TNFalpha genes compared with their coinduction when both receptor pathways are activated
Yadav et al., Blood 2006
:
We determined that mitogen activated protein kinase ( MAPK ) activation and
tumor necrosis factor-alpha (TNF-alpha) production in macrophage infected with Mycobacterium avium or M smegmatis is
dependent on myeloid differentiation factor 88 ( MyD88 ) and TLR2 but not
TLR4 , MR, or CR3
Levy et al., J Immunol 2006
:
The adenosine system selectively inhibits
TLR mediated
TNF-alpha production in the human newborn ... Selective inhibition of neonatal TNF-alpha production is due to the distinct neonatal adenosine system, including relatively high adenosine concentrations in neonatal blood plasma and heightened sensitivity of neonatal mononuclear cells to adenosine A3 receptor mediated accumulation of cAMP, a second messenger that inhibits
TLR mediated
TNF-alpha synthesis but preserves IL-6 production
Juarranz et al., Ann N Y Acad Sci 2006
:
VIP decreases
TLR4 expression
induced by LPS and
TNF-alpha treatment in human synovial fibroblasts
Sanchez-Perez et al., J Immunol 2006
(Melanoma, Experimental...) :
We show in this study that, in that regimen, hsp70 acts as a potent immune adjuvant through
TLR-4 signaling and local
induction of
TNF-alpha
Ramakers et al., Cytokine 2006
:
CGS21680 inhibited
TLR4 mediated
TNF-alpha release and potentiated TLR3- and TLR5 mediated IL-6 release
Ji et al., Zhong Xi Yi Jie He Xue Bao 2006
:
HXR could down-regulate the expression of membrane receptor
TLR4 and
inhibit the expressions of NF-kappaB and
TNF-alpha ... QGHXR could down regulate the expressions of membrane receptors CD14 and
TLR(4) and
inhibit the expressions of NF-kappaB and
TNF-alpha ... QGHXR can protect liver cells by down regulating the expressions of CD14,
TLR(4) and NF-kappaB and
inhibiting TNF-alpha expression
Mohri et al., J Trauma 2006
(Systemic Inflammatory Response Syndrome) :
Expression of HO-1,
TLR2 , and TLR4 in monocytes was significantly
enhanced in patients with severe SIRS compared with that in healthy volunteers, whereas intracellular
TNF-alpha expression with peptidoglycan was significantly decreased ( p < 0.05 ) in patients compared with that in healthy volunteers
Grandjean-Laquerriere et al., Biomaterials 2007
(Inflammation) :
Our data clearly show for the first time that the production of
TNF-alpha by macrophages exposed to HA particles was
TLR4 dependent but not the activation of NF-kappaB
Shahrara et al., J Immunol 2006
(Arthritis, Rheumatoid...) :
Because endogenous TLR4 ligands are expressed in the rheumatoid joint, the TLR4 ligand LPS was used to characterize the effects of RANTES on the
TLR4 mediated induction of
TNF-alpha and IL-6 ... In conclusion, the results of this study suggest that RANTES down-regulates
TLR4 ligation
induced IL-6 and
TNF-alpha secretion by enhancing IL-10 production in PB monocytes
Broad et al., Immunology 2007
:
In this study we have shown that, whilst NF-kappaB activation and production of
TNF-alpha and interleukin-12 by murine RAW264.7 and J774.2 cells in response to stimulation by TLR4, -5, -7 or -9, was reduced by prior
stimulation with
TLR4 , -5, -7 or -9 ligands, the primary stimulation of TLR3, which does not use the MyD88 pathway, did not reduce the TNF-alpha or interleukin-12 responses to subsequent TLR stimulation
Gao et al., Zhonghua Yan Ke Za Zhi 2006
:
The activity of IkappaBalpha in THCE cells was decreased to 10.31 +/- 1.30 ( gray scale value ) and 8.15 +/- 2.37 at 30 min after challenged with AF mycelium or supernatant extract agent compared to 51.57 +/- 5.58 and 49.23 +/- 3.49 of control group ( P < 0.01 ), and was reverted at 2 h. The secretion of IL-8 and
TNF-alpha was partly
inhibited by blocking TLR2 or
TLR4 ( P < 0.05 ), obviously inhibited by blocking TLR2 and TLR4 ( 50 % and 40 % compared to that of control group ) ( P < 0.01 ) when challenged with AF mycelium. And that was markedly inhibited by blocking TLR4 or blocking TLR2 and TLR4 when challenged with AF supernatant ( P < 0.01 ). The secretion of IL-8 and TNF-alpha was not inhibited by blocking TLR2 when challenged with AF supernatant ( P > 0.05 )
Wang et al., Blood 2007
:
Here we demonstrate that Rab7b can negatively
regulate lipopolysaccharide (LPS) induced production of
tumor necrosis factor (TNF)-alpha , IL-6, nitric oxide, and IFN-beta, and potentiate LPS induced activation of mitogen activated protein kinase, nuclear factor kappaB, and IFN regulatory factor 3 signaling pathways in macrophages by promoting the degradation of
TLR4
Moeinpour et al., Mol Immunol 2007
(Hemorrhage...) :
Trauma-hemorrhage increased the production of IL-6, IL-10, IL-12 and
TNF-alpha enhanced the expression of
TLR4 , MyD88 as well as the activation of MAPK proteins ( p38, ERK and JNK ) in epidermal keratinocytes
Hung et al., Biochem Pharmacol 2007
:
CCL-34 activated NF-kappaB in a
TLR4 dependent manner and stimulated
TNF-alpha production in bone marrow cells of TLR4-functional C3H/HeN mice but not in those of TLR4-defective C3H/HeJ mice
Kim et al., Immunol Lett 2007
(Arthritis, Rheumatoid...) :
TLR stimulation of RA-FLS also
induced the production of IL-1beta and
TNF-alpha to a lesser extent ; however, it had no effect on IL-17 production
Loniewski et al., Mol Immunol 2007
:
Compared to the signaling data, while
TLR4 induced
TNFalpha mRNA expression is not significantly inhibited by TRAF6 knockdown, TLR7 induced TNFalpha mRNA is significantly blocked
Shu et al., Clin Exp Immunol 2007
:
natural killer ( NK ) 1.1 ( - ) CD11c ( + ) liver DC subsets ( conventional DCs, T cell receptor ( TcR ) beta ( - ) NK1.1 ( - ) CD11c ( + ) B220 ( - ) and plasmacytoid DCs, TcRbeta ( - ) NK1.1 ( - ) CD11c ( + ) B220 ( + ) ) efficiently endocytose dextran and produce significant levels of
tumour necrosis factor (TNF)-alpha , interleukin (IL)-6 and IL-12 p40 in
response to
Toll-like receptor ( TLR ) ligands, with responses higher than splenic DCs
Koval'chuk et al., Zh Mikrobiol Epidemiol Immunobiol 2007
(Common Variable Immunodeficiency) :
Spontaneous production of TNF-alpha by PBMC in patients with CVID was increased and accompanied by decrease in TNF-alpha production stimulated by each analyzed ligands except CpG. Observed changes in
TLR dependent
TNF-alpha production can play important role in pathogenesis of CVID
Yu et al., Int Immunopharmacol 2007
(Sepsis) :
Ketamine 2.5, 5 and 10 mg/kg after CLP decreased intestinal
TNF-alpha level and NF-kappaB activity, and
inhibited TLR2 and
TLR4 expressions as well
Szabo et al., Pancreatology 2007
(Pancreatitis, Alcoholic) :
Prolonged alcohol exposure also resulted in an increase in NF-kappaB and
TNFalpha production in
response to
TLR4 stimulation with LPS
Sá-Nunes et al., J Immunol 2007
:
Saliva at remarkably diluted concentrations ( < 1/2000 ) promotes a dose dependent inhibition of IL-12 and
TNF-alpha production
induced by all
TLR ligands used
Ferwerda et al., J Leukoc Biol 2007
(Crohn Disease) :
TLR induced
TNF-alpha , IL-1beta, and IL-10 production is mediated through MyD88, whereas Toll-IL-1R domain containing adaptor inducing IFN-beta ( TRIF ) promoted the release of IL-1beta
Cavaleiro et al., Eur J Immunol 2007
:
The TLR4 pathway is likely involved, since gp105 activates
TLR4 signaling and
induces TNF-alpha production by monocytes
Kullberg et al., Immunology 2008
(Crohn Disease...) :
While in cells isolated from patients with Crohn 's disease with the wild-type NOD2 allele, the NOD2 engagement led to a similar cross-tolerance to
TLR4 dependent stimulation of
TNF-alpha , the cross-tolerance between NOD2 and TLR4 was absent in the cells of five patients homozygous for the 3020insC NOD2 mutation, leading to uninhibited release of TNF-alpha by TLR4 ligands and intestinal bacteria
Wilson et al., Cell Microbiol 2008
:
Production of
TNF-alpha and IL-6 was
dependent on expression of
TLR4 as stimulation of macrophages from TLR4 ( -/- ) mice with S. Typhimurium did not result in expression of these cytokines
Koval'chuk et al., Bull Exp Biol Med 2007
(Common Variable Immunodeficiency) :
Reduced stimulated production of
TNF-alpha in
response to stimulation with
TLR4 and TLR5 ligands in vitro was detected in patients with common variable immunodeficiency
Yu et al., Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques 2007
(Pneumonia...) :
Ketamine at sub-anesthetic doses could suppress the production of inflammatory cytokines such as
TNF-alpha and IL-6, attenuate NF-kappaB activity, and
inhibit TLR2 and
TLR4 expression in polymicrobial sepsis
Taneichi et al., Clin Immunol 2008
(Agammaglobulinemia...) :
Stimulation with TLR2,
TLR4 and TLR7/8 ligands, as well as TLR3 ligand,
resulted in significantly lower production of
TNF-alpha , but neither IL-6 nor IL-12p70, by DCs from XLA patients in comparison to normal controls
Cha et al., Ann Thorac Surg 2008
(Myocardial Reperfusion Injury) :
This study examined whether
TLR4 regulates
TNF-alpha and interleukin (IL)-1beta peptide production during global ischemia/reperfusion and whether TLR4 signaling influences postischemic cardiac function through TNF-alpha and IL-1beta
Nicol et al., J Virol 2008
(HIV Infections) :
AMs from HIV positive subjects also showed decreased
TNF-alpha production in
response to these TLR2 and
TLR4 ligands
Prescott et al., J Allergy Clin Immunol 2008
(Hypersensitivity...) :
Maternal allergy ( n = 59 ) was associated with significantly higher neonatal IL-12 and IFN-gamma responses to TLR2, TLR3, and TLR4 activation, whereas
TNF-alpha and IL-6
responses to TLR2,
TLR4 , and TLR5 activation were significantly higher in newborns who subsequently had allergic disease ( n = 32 )
Farkas et al., Scand J Immunol 2008
:
Our study provides evidence that NOD2,
toll-like receptor 4 (TLR4) and the adapter protein receptor interacting protein 2 (RIP2) are
induced by
tumor-necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the bronchial epithelial cell line BEAS-2B
Jiang et al., Virology 2008
(Hemorrhagic Fever with Renal Syndrome) :
The increased IFN-beta, IL-6 and
TNF-alpha production was
mediated by
TLR4 induction, since the introduction of the small interfering RNA against TLR4 specifically inhibited the HTNV induced cytokine production ... In conclusion, HTNV infection directly
induces TLR4 expression and thereby enhanced production of IFN-beta, IL-6 and
TNF-alpha , which may contribute to the host 's innate immune response
Behrens et al., J Immunol 2008
:
A number of recent studies show that activation of CR3 on dendritic cells (DCs) suppresses
TLR induced
TNF-alpha and IL-12 production and inhibits effective Ag presentation ...
TLR induced
TNF-alpha and IL-12 production by bone marrow derived DCs occurs heterogeneously, with apoptotic cells inhibiting only certain populations depending on the TLR agonist
Croker et al., Proc Natl Acad Sci U S A 2008
(Autoimmune Diseases...) :
TLR induced
TNF and IL-1 production are normal in macrophages derived from spin mice
Tachado et al., J Biol Chem 2008
(HIV Infections...) :
Constitutive activation of phosphatidylinositol 3-kinase signaling pathway down-regulates
TLR4 mediated
tumor necrosis factor-alpha release in alveolar macrophages from asymptomatic HIV positive persons in vitro ... In the current study, surface TLR4 expression were similar but
TLR4 activation ( lipid A, 10 microg/ml )
resulted in lower
TNF-alpha release by HIV+ human macrophages compared with healthy cells
Mencarelli et al., Am J Physiol Heart Circ Physiol 2009
(Atherosclerosis...) :
FXR activation by natural and synthetic ligands in these cell types attenuated IL-1beta, IL-6, and
TNF-alpha gene induction in
response to
Toll-like receptor 4 activation by LPS
Roychowdhury et al., Hepatology 2009
(Hepatitis, Alcoholic) :
In contrast, the absence of
Toll-like receptor 4 (TLR-4) had no effect on the early, ethanol induced increase in either C3b or
TNF-alpha
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
Mishra et al., Immunobiology 2009
:
Our findings suggest that RAE
induces TLR-4 expression and intracellular granzyme-B in treated splenocytes while RAE stimulated IL-1beta, IL-6, and
TNF-alpha in human PBMCs
Huang et al., Infect Immun 2009
:
These two beta-glucans failed to stimulate TNF-alpha in Dectin-1 ( beta-glucan receptor ) knockout BMDCs. Costimulation of wild-type BMDCs with beta-glucans and specific
Toll-like receptor ( TLR ) ligands
resulted in greatly enhanced
TNF-alpha production but decreased IL-12p70 production compared with TLR agonists alone
Matsushita et al., Nature 2009
(Anemia...) :
Macrophages from Zc3h12a ( -/- ) mice showed highly increased production of interleukin (IL)-6 and IL-12p40 ( also known as IL12b ), but not
TNF , in
response to
TLR ligands
Chaung et al., Vet Immunol Immunopathol 2009
:
Zymosan
enhanced dectin-1/TLR2/TLR4 expression and TNF-alpha/IL-10 production in all of three types of cell, whereas p-beta-glucan increased dectin-1/TLR4 and
TNF-alpha/IL-12 production in AMs but inhibited IL-10 in mDCs
Jung et al., Immunol Lett 2009
(Arthritis, Experimental...) :
The aim of this study was to determine whether stimulation of toll-like receptor 2 (TLR2),
TLR4 , and TLR6 by their specific ligands
induces the production of
tumor necrosis factor-alpha (TNF-alpha) in fibroblast-like synoviocytes ( FLS ) from interleukin-1 receptor antagonist ( IL-1Ra ) -deficient mice ... Stimulation of TLR2,
TLR4 , and TLR6 by their specific ligands
increased the production of
TNF-alpha in FLS from IL-1Ra-deficient mice ... These data show that TLR2,
TLR4 , and TLR6 ligation synergistically
stimulates the production of
TNF-alpha and IL-1beta in IL-1Ra-deficient mice and suggest that TLRs contribute to the perpetuation of spontaneous arthritis in this animal model
Covacu et al., J Immunol 2009
:
TLR activation
induces TNF-alpha production from adult neural stem/progenitor cells
Siegemund et al., J Virol 2009
:
In contrast, iPPVO induced
TNF-alpha release and enhanced expression of MHC-I and CD86 but not of MHC-II by BMDC chiefly
requires MyD88 but not TLR2 or
TLR4
Shi et al., Clin Exp Pharmacol Physiol 2010
(Atherosclerosis...) :
Although the baseline expression of Toll-like receptor (TLR) 4 was low in both HAEC and BAEC,
TNF-alpha activated
TLR4 expression in both cell types
Cho et al., PloS one 2009
(Inflammation) :
Utilizing this cell line, we screened a completely random lentiviral short hairpin RNA ( shRNA ) library for sequences that inhibited
TLR mediated
TNF-alpha production ... Recovery of shRNA sequences from surviving cells led to the identification of unique shRNA sequences that significantly inhibited
TLR4 dependent
TNF-alpha gene expression
Fraser et al., Exp Hematol 2009
:
The production of
TNF-alpha was also impaired in vitro in
response to TLR3,
TLR4 , and TLR9 stimulation of the mouse macrophage cell line RAW264.7, as well as TLR4 and TLR9 stimulation of BMDM ; IL-6 production was also impaired in dasatinib treated BMDM
West et al., Infect Immun 2009
(Burkholderia Infections...) :
In macrophages,
TLR4 and the adaptor molecule MyD88, but not TLR2 or TLR5, are
required for
tumor necrosis factor alpha production induced by B. thailandensis
Frazier et al., J Immunol 2009
(Escherichia coli Infections...) :
MAPKs are crucial for
TNF-alpha and IL-6 production by innate immune cells in
response to
TLR ligands
Caron et al., Neonatology 2010
:
In contrast, TLR stimulated proinflammatory cytokine production was markedly higher in neonates than in adults, with the exception of
TLR-4 induced
TNF-alpha production
Testro et al., J Hepatol 2010
(Gram-Negative Bacterial Infections...) :
TLR4 dependent
TNF-alpha production increased following antibiotic use ( 1077 vs. 3620pg/mL, p < 0.05 ), whilst TLR2 dependent production was unchanged
van Hoffen et al., Int Arch Allergy Immunol 2010
:
Apically added LGG,
TLR2 and NOD2 ligands, but not Bb,
enhanced IFN-gamma, IL-12 and/or
TNF-alpha secretion
Riddell et al., J Immunol 2010
:
In the current study, we demonstrate that incubation of Prx1 with thioglycollate elicited murine macrophages or immature bone marrow derived dendritic cells resulted in
TLR4 dependent secretion of
TNF-alpha and IL-6 and dendritic cell maturation
Stamm et al., FEMS Immunol Med Microbiol 2010
(Vibrio Infections) :
Results obtained using V. vulnificus type strain ATCC 27562 showed that ( 1 ) TLR4 signaling is myeloid differentiation factor 88 dependent and plays a key role in TNFalpha production by mouse blood and splenocytes stimulated ex vivo with inactivated V. vulnificus cells, ( 2 ) TLR4 signaling is deleterious in a mouse model of V. vulnificus infection, ( 3 ) signaling by TLR ( s ), exclusive of TLR4, is needed to eradicate infection, and ( 4 ) the
TLR mediated
TNFalpha response plays a critical role in determining the outcome of infection
Deopurkar et al., Diabetes Care 2010
(Inflammation) :
Indexes of inflammation including nuclear factor-kappaB (NF-kappaB) binding, and the expression of SOCS3,
tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-1beta in MNCs, increased significantly after glucose and cream intake, but
TLR-4 expression and plasma LPS concentrations
increased only after cream intake
Sheng et al., Acta Cardiol 2009
(Dilatation, Pathologic...) :
The expression of TLR4,
TNF-alpha and IL-6 in the myocardium significantly
increased in the MI group and simvastatin markedly inhibits the expression of
TLR4 , TNF-alpha, and IL-6 in the myocardium after MI. Serum TNF-alpha and IL-6 levels between the MI group and the simvastatin group remained unchanged
Tachado et al., Blood 2010
(HIV Infections...) :
TLR4 mediated
tumor necrosis factor alpha (TNFalpha) release is significantly impaired in HIV ( + ) macrophages, but whether HIV impairs myeloid differentiation factor 88 ( MyD88 ) -dependent and/or MyD independent TLR4 signaling pathways in human macrophages is not known
Shyu et al., J Biomed Sci 2010
:
TNF-alpha and Ang II significantly
increased TLR4 protein expression
Koval'chuk et al., Zh Mikrobiol Epidemiol Immunobiol 2010
(Pancreatitis, Acute Necrotizing) :
Patients with AP demonstrated increased production of
TNFalpha induced by TLR1/2 and
TLR4 ligands
Sashinami et al., FEMS Immunol Med Microbiol 2010
(Listeriosis) :
Toll-like receptor 4 may be
involved in
TNF-alpha production from RAW264.7 cells and enhanced host resistance induced by p60 administration
Fang et al., FEMS Immunol Med Microbiol 2010
(West Nile Fever) :
Viral antigens were detected in WNV infected gammadelta T cells.WNV infection or
toll-like receptor ( TLR ) agonist treatment of gammadelta T cells
induced the production of IFN-gamma,
tumor necrosis factor-alpha and IL-6, which are known to promote DC maturation
Bhan et al., PloS one 2010
(Pneumonia, Bacterial) :
Early lung expression of
TNF-alpha , IL-12, and chemokines was
TLR4 dependent , while IFN-gamma production and the later expression of TNF-alpha and IL-12 was dependent on TLR9
Gais et al., J Immunol 2010
(MAP Kinase Signaling System) :
Importantly, stimulation of Mk2 ( -/- ) cells through TLR3 or
TLR4 severely
impaired TNF-alpha protein production but did not affect TNF-alpha mRNA induction
Panaro et al., Curr Pharm Des 2010
:
Toll-like receptor 4 mediates LPS induced release of nitric oxide and
tumor necrosis factor-alpha by embryonal cardiomyocytes : biological significance and clinical implications in human pathology ... It will be reported that LPS is able to
induce TNF-alpha and NO release from cultured cardiomyocytes, while molecular and morphological evidence demonstrates the expression of
TLR4 on surface membrane of embryonal cardiomyocytes
Oliveira et al., PLoS Pathog 2010
(Chagas Disease) :
Our studies demonstrated that
TLR4 signaling is
required for optimal production of IFN-gamma,
TNF-alpha and nitric oxide ( NO ) in the spleen of infected animals and, as a consequence, Tlr4 ( -/- ) mice display higher parasitemia levels
Gasparoto et al., Med Mycol 2010
(Candidiasis...) :
Our results show that the absence of functional
TLR4 resulted in lower chemotaxis of neutrophils to the site of infection, lower levels of
TNF-a , CXCL1 and nitric oxide, and dissemination and persistence of the pathogen in lymph nodes and spleen
Chávez-Sánchez et al., Hum Immunol 2010
:
Our results suggest that mmLDL activates CD14,
TLR4 , and TLR2,
inducing the production of
TNF-alpha and increasing the expression of TLR2 and TLR4
He et al., J Cell Biochem 2010
:
The activation of
TLR4 by LPS modulated the expression of TLRs, induced the phosphorylation of NF-kappaB, P38, and ERK42/44, and
up-regulated the gene expression of cytokines IL-8, IFN-alpha, IFN-beta, and
TNF-alpha , suggesting EPCs expressed functional TLR4
Chen et al., J Biomed Sci 2010
(Burns) :
Commensal depletion decreased
TLR4 expression as well as NF-kappaB
activation of intestine, myeloperoxidase (MPO) activity as well as
TNFalpha expression of lung, and bacterial killing activity of peritoneal cells
Yang et al., Proc Natl Acad Sci U S A 2010
:
Here we show that
Toll-like receptor 4 (TLR4) , a pivotal receptor for activation of innate immunity and cytokine release, is
required for HMGB1 dependent activation of macrophage
TNF release ... A wholly synthetic 20-mer peptide containing cysteine 106 from within the cytokine stimulating B box mediates
TLR4 dependent activation of macrophage
TNF release
Pan et al., Zhong Xi Yi Jie He Xue Bao 2010
(Colitis) :
Up-regulating the expression of occludin and down
regulating the expressions of
TLR4 and NF-kappaB, and hence inhibiting
TNF-alpha expression and improving the mucosa barrier function may be part of the mechanisms of BWXLS in treating oxazolone induced colitis in mice
Mureith et al., AIDS 2010
(Disease Progression...) :
Responses by THP-1 cells to TLR stimulation were quantified using Quanti-Blue colometric assay, and
TLR induced
tumor necrosis factor-alpha production of primary monocytes was quantified by intracellular cytokine staining using flow cytometry
Liu et al., Inflammation 2011
(Atherosclerosis) :
TLR4 knockdown significantly
inhibited CRP induced
TNF-a generation, and p38 mitogen activated protein kinase ( MAPK ) blocker SB203580 depressed TLR4 expression and TNF-a production initiated by CRP in VSMCs
de Kivit et al., Immunobiology 2011
(Inflammation) :
TLR4 ligation of IEC ( HT-29 )
enhanced the production of
TNF-a and IEC derived MDC and decreased numbers of Foxp3 ( + ) regulatory T cells ... Neutralization of TSLP abrogated
TLR4 induced
TNF-a secretion
Sokolove et al., Arthritis Rheum 2011
(Arthritis, Rheumatoid...) :
Stimulation of
TNF by cFb was
dependent on
TLR-4 and MyD88, while stimulation by cFb-IC was dependent on both TLR-4/MyD88 and Fc?R
Yan et al., Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 2010
:
To characterize the
role of
Toll-like receptor 4 (TLR4) in silica induced production of
tumor necrosis factor alpha (TNFalpha) from macrophage cell line ... To examine the
involvement of
TLR4 in silica induced
TNFalpha release, the neutralizing antibody ( HTA125 ) against human TLR4 receptor was employed to pretreat THP-1 cells prior to silica treatment ...
TLR4 mediates silica induced
TNFalpha release from macrophages
Song et al., Leukemia 2011
:
LBH589 also significantly repressed the production of interleukin (IL)-6, IL-10, IL-12p70, IL-23 and
tumor necrosis factor-a by Toll-like receptor (TLR)3 and
TLR4 induced DC
activation , indicating an important role of HDAC activity in immune regulation and inflammation
Testro et al., J Gastroenterol Hepatol 2011
(Acute Disease) :
Post-transplant, the two groups differed with regard to
TLR4 dependent
TNF-a production, with rejectors demonstrating progressive downregulation over the first week
Kar et al., Eur J Immunol 2011
(Inflammation...) :
Analysis of upstream signaling events revealed that
TLR 2/4 mediated MyD88 dependent participation of IL-1R activated kinase (IRAK)1,
TNF receptor associated factor (TRAF)6 and TGFß activated kinase (TAK)1 is essential to induce cystatin mediated I?B kinase ( IKK ) /NF-?B activation in macrophages
El-Hage et al., Immunol Invest 2011
:
TLR3 and
TLR4 stimulation
increased the secretion of
TNF-a , IL-6, and RANTES/CCL5, while activation of TLR2 caused a significant increase in nitric oxide levels
Wheeler et al., Advances in pharmacological sciences 2011
:
Albumin produced a dose dependent and
TLR-4 dependent increase in NF-?B activation and
TNF-a gene expression in vitro
Caraş et al., Roum Arch Microbiol Immunol 2011
:
As expected, induction of
TNF-alpha and IL-6 by TLR4 agonist LPS was
inhibited in a significant manner by
anti-TLR4 but not by anti-TLR2 antibody
Minematsu et al., Cell Signal 2011
:
Treatment with VIVIT resulted in nuclear export of NFATc3/c4 and inhibited
TLR activated
TNF expression, suggesting that nuclear residence of NFATc is required for TLR related innate immune response
Das et al., Immunol Cell Biol 2012
(Leishmaniasis, Visceral) :
In this report, we demonstrated that later stages of L. donovani infection rendered tolerance to macrophages, leading to incapability for the production of inflammatory cytokines like
tumor necrosis factor (TNF)-a and interleukin (IL)-1ß in
response to
TLR stimulation
Li et al., J Immunol 2011
(HIV Infections...) :
Mammalian target of rapamycin inhibition in macrophages of asymptomatic HIV+ persons reverses the decrease in
TLR-4 mediated
TNF-a release through prolongation of MAPK pathway activation ... In this study we assessed in these macrophages if the blunted increase in
TLR-4 mediated
TNF-a release induced by lipid A ( LA ) is associated with PI3K induced upregulation of mammalian target of rapamycin (mTOR) activity ... mTOR inhibition with rapamycin enhanced
TLR-4 mediated
TNF-a release, but suppressed anti-inflammatory IL-10 release ... Targeted gene silencing of MyD88 ( short hairpin RNA ) and mTOR ( RNA interference ) inhibition resulted in
TLR-4 mediated 70-kDa ribosomal protein S6 kinase activation and enhanced
TNF-a release, whereas IL-10 release was inhibited in both silenced and nonsilenced HIV ( + ) macrophages
Farrar et al., FASEB J 2012
(Disease Models, Animal...) :
Activation of
TLR leads to activation of NF-?B and release of proinflammatory cytokines, such as IL-6 and
TNF-a
Fortes et al., Blood 2012
(Necrosis) :
Heme induces
TLR4 dependent production of
tumor necrosis factor (TNF) , whereas heme cytotoxicity has been attributed to its ability to intercalate into cell membranes and cause oxidative stress ... Heme induced cell death required TNFR1 and
TLR4/MyD88 dependent
TNF production
Avila et al., Innate Immun 2012
:
Our results indicate that Lyn plays a positive role in
TLR4 induced production of
TNF-a in MCs controlling the activity of the TRAF-6/TAK-1 protein complex
von Maltzan et al., PloS one 2012
:
The current study was designed to investigate the mechanisms of this effect by determining whether ethanol inhibits TLR3 and
TLR4 mediated
TNF-a secretion through inhibition of transcription factor activation or post-transcriptional effects
Kim et al., J Nutr Biochem 2012
(Myocardial Infarction...) :
In CMs,
TLR2 and monocyte chemoattractant protein (MCP)-1 mRNAs were
increased by
TNF-a , PGN or H/R, whereas they were blunted by curcumin
Panda et al., J Reprod Immunol 2012
(Pre-Eclampsia) :
The expression of
TLR induced production of
TNF-a , IFN-a, IL-6, and IL-12 were measured by multicolor flow cytometry
Movita et al., J Leukoc Biol 2012
:
Interestingly, despite expression of TLR mRNA on Kupffer cells, ligation of TLR4,
TLR7/8 , and TLR9
resulted in a weak induction of IL-10, low or undetectable levels of IL-12p40 and
TNF , and up-regulation of CD40 on the surface
Villacres et al., J Infect Dis 2012
(HIV Infections...) :
Peripheral blood mononuclear cells ( PBMCs ) obtained at baseline were used to measure interleukin 1ß (IL-1ß), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 12 (IL-12), and
tumor necrosis factor a (TNF-a) responses to Toll-like receptor (TLR) 3 and
TLR4 stimulation
Boswell et al., Immunobiology 2013
:
Induction of CD152 ( CTLA-4 ) and LAP ( TGF-ß1 ) in human Foxp3 ( - ) CD4 ( + ) CD25 ( - ) T cells modulates
TLR-4 induced
TNF-a production
Das et al., J Antimicrob Chemother 2012
:
Both drugs, as monotherapy or in combination, induce release of
TNF-a and nitric oxide in a
TLR4 dependent manner ... In vitro, both the drugs kill macrophage bound L. donovani by inducing release of
TNF-a and nitric oxide in a
TLR4 dependent manner
Bala et al., J Leukoc Biol 2012
:
We found that acute alcohol pretreatment resulted in the same attenuating effect as LPS pretreatment on
TLR4 induced
TNF-a production in human monocytes and murine RAW 264.7 macrophages
Lee et al., Invest Ophthalmol Vis Sci 2012
(Disease Models, Animal...) :
TLR4 inhibition decreased the severity of CFS and significantly
reduced the mRNA expression of IL-1ß, IL-6, and
TNF
Kawahara et al., Exp Cell Res 2012
:
MMCH clones also expressed Toll-like receptors ( TLRs ) 1, 2, 4, and 6 and showed elevated levels of
TNF-a expression in
response to stimulation with TLR2 and
TLR4 ligands
Ding et al., Gene 2012
(Myocardial Reperfusion Injury) :
The results demonstrated that fewer neutrophils infiltrated in the myocardium of TLR4-mutant mice after myocardial I/R and that
TLR4 deficiency markedly decreased the ischemic injury caused by ischemia/reperfusion, and
inhibited the expression of HMGB1,
TNF-a , and IL-8, all of which were up-regulated by ischemia/reperfusion
Hilda et al., FEMS Immunol Med Microbiol 2012
:
Increased expression of CD32, CD64,
TLR4 , and CXCR3 ;
increased TNF-a secretion ; and downregulation of early apoptosis were observed in H37Rv infected neutrophils
Kim et al., Microb Pathog 2013
:
In addition,
TLR4 was
required for the optimal production of IL-6,
TNF-a , and IL-12 in BMDCs in response to A. baumannii
Deng et al., Immunol Cell Biol 2013
:
Further, we demonstrated that
TLR induced
tumor necrosis factor-a and interferon-ß contributed to the differential phagocytosis of apoptotic neutrophils and bacteria by macrophages
Cox et al., PloS one 2012
:
Hb alone can elicit the
TLR4 dependent secretion of
TNF-a from macrophages, so it may be the TLR4 ligand
Papadopoulos et al., J Immunol 2013
(Alveolar Bone Loss...) :
Whereas both TLR2 and
TLR4 contributed to
TNF production in naive macrophages, P. gingivalis preferentially exploited TLR2 in endotoxin-tolerant BMDM to trigger excessive TNF production
Karrich et al., Blood 2013
:
Although IL-21 did not affect
TLR induced type I IFNs, IL-6, and
TNF-a nor expression of major-histocompatibility-complex class II or costimulatory molecules, IL-21 markedly increased expression of the serine protease granzyme B (GrB)
Ferrante et al., Inflammation 2013
:
Adenosine signaling suppresses the
TLR dependent expression of
TNF-a , IL-12, IFN-?, and several other inflammatory cytokines by macrophages and induces the expression of vascular endothelial growth factor ( VEGF ) and IL-10
Liu et al., Scand J Immunol 2013
:
Our results demonstrate that not only TLR2 but also TLR4 and RP105 are involved in the response of macrophages to S. aureus, that TLR2, TLR4 and RP105 physically interact with each other during S. aureus infection, and that TLR2,
TLR4 and RP105 both cooperate and
play unique roles in the production of inflammatory cytokines (
TNF-a , IL-12p40 and IL-10 ) and chemokine ( RANTES ) by macrophages after S. aureus infection
Pedraza-Sánchez et al., Clinical and vaccine immunology : CVI 2013
:
Thus, a reduced CD14 ( + ) CD16 ( + ) activated/differentiated monocyte subset and a correspondingly lower level of functional
TLR4 on monocytes
contributes to the relatively low
TNF-a response to LPS observed in immunologically naive newborns compared to the response in adults
Czerkies et al., Immunobiology 2013
:
These data indicate that SR-A is
required for maximal production of
TNF-a in cells stimulated with LPS, possibly by modulating the cell surface levels of
TLR4 and CD14
Hilbert et al., PloS one 2013
:
TLR9 induced IFNA1 secretion as well as
TLR4 induced
TNF secretion from PBMCs was dose-dependently attenuated by coincubation with epinephrine
Brancato et al., Wound Repair Regen 2013
(Disease Progression...) :
The accumulation of CCL2, CX3CL1,
tumor necrosis factor-a , interleukin (IL)-6, IL-10, IL-12, and interferon-? in wound fluids was not
TLR4 dependent
Liu et al., J Neurosci 2013
:
In cultured neurons,
TLR7 activation
induced IL-6 and
TNF-a expression through Myd88
Römmler et al., J Immunol 2013
:
Whereas TLR9 induced TNF-a secretion of bone marrow derived macrophages and conventional dendritic cells was equally inhibited by INH-ODN 2088 and G-modified INH-ODNs such as INH-ODN 24888,
TLR7 induced
TNF-a release and TLR7- and TLR9 induced IL-12p40 release were significantly more impaired by G-modified INH-ODNs