INT7535

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Context Info
Confidence 0.56
First Reported 1985
Last Reported 2011
Negated 1
Speculated 2
Reported most in Body
Documents 111
Total Number 114
Disease Relevance 56.84
Pain Relevance 21.37

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

signal transduction (Tlr4) plasma membrane (Tlr4) intracellular (Tlr4)
cytoplasm (Tlr4)
Anatomy Link Frequency
macrophages 6
brain 2
monocyte 2
lung 2
neurons 2
Tlr4 (Mus musculus)
Pain Link Frequency Relevance Heat
Inflammation 2312 100.00 Very High Very High Very High
Dopamine 175 100.00 Very High Very High Very High
Intracerebroventricular 40 100.00 Very High Very High Very High
Pain 37 100.00 Very High Very High Very High
cytokine 1389 99.96 Very High Very High Very High
local anesthetic 12 99.90 Very High Very High Very High
adenocard 129 99.84 Very High Very High Very High
tolerance 105 99.84 Very High Very High Very High
midbrain 30 99.84 Very High Very High Very High
agonist 202 99.68 Very High Very High Very High
Disease Link Frequency Relevance Heat
INFLAMMATION 2526 100.00 Very High Very High Very High
Burns 454 100.00 Very High Very High Very High
Chlamydia Infection 69 100.00 Very High Very High Very High
Pain 39 100.00 Very High Very High Very High
Bacteremia 30 100.00 Very High Very High Very High
Pseudomonas Infection 22 100.00 Very High Very High Very High
Lumbar Puncture Related Headaches 5 100.00 Very High Very High Very High
Apoptosis 217 99.96 Very High Very High Very High
Enteropathy 4 99.92 Very High Very High Very High
Alzheimer's Dementia 67 99.80 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
A mouse model of MI has recently shown that inhibition of TLR4 with its antagonist attenuates the inflammatory response to MI, as shown by a significant decrease in infarct size and expression of inflammatory mediators [33].
Negative_regulation (inhibition) of TLR4 associated with inflammatory mediators, inflammatory response and antagonist
1) Confidence 0.56 Published 2008 Journal Clinical Science (London, England : 1979) Section Body Doc Link PMC2552974 Disease Relevance 0.55 Pain Relevance 0.39
It therefore acts as a physiological inhibitor of TLR4 signalling.
Negative_regulation (inhibitor) of TLR4
2) Confidence 0.51 Published 2010 Journal Mediators of Inflammation Section Body Doc Link PMC2855078 Disease Relevance 0.13 Pain Relevance 0
Inhibition of toll-like receptor-4, nuclear factor-kappaB and mitogen-activated protein kinase by lignocaine may involve voltage-sensitive sodium channels.
Negative_regulation (Inhibition) of toll-like receptor-4 associated with sodium channel
3) Confidence 0.44 Published 2008 Journal Clin. Exp. Pharmacol. Physiol. Section Title Doc Link 18505446 Disease Relevance 0.18 Pain Relevance 0.34
Oral antibiotics treatment significantly decreased TLR4 protein (Figure 4A) and mRNA (Figure 4B) expression of intestinal mucosa in burn mice compared with burn only group.
Negative_regulation (decreased) of TLR4 protein associated with burns
4) Confidence 0.43 Published 2010 Journal J Biomed Sci Section Body Doc Link PMC2901327 Disease Relevance 0.81 Pain Relevance 0
Our data demonstrate that commensal depletion significantly decreases TLR4 as well as TNF?
Negative_regulation (decreases) of TLR4
5) Confidence 0.43 Published 2010 Journal J Biomed Sci Section Body Doc Link PMC2901327 Disease Relevance 1.20 Pain Relevance 0.11
Oral antibiotics significantly decreased TLR4 and TNF?
Negative_regulation (decreased) of TLR4
6) Confidence 0.43 Published 2010 Journal J Biomed Sci Section Body Doc Link PMC2901327 Disease Relevance 1.34 Pain Relevance 0.05
The targeted pharmacologic inhibition of TLR4 in the clinical setting of myocardial ischemia and reperfusion could initially lead to a smaller infarct, but an altered inflammatory response could have unexpected effects on cardiac function and long term infarct healing.
Negative_regulation (inhibition) of TLR4 associated with ischemic heart disease, inflammatory response and ischemia
7) Confidence 0.42 Published 2007 Journal BMC Physiol Section Body Doc Link PMC1933437 Disease Relevance 1.33 Pain Relevance 0.34
However, we did not observe differences in myocardial cytokines between WT and C3H/HeJ MI/R, except for IL-6, which was significantly decreased in TLR4-deficient MI/R mice.
Negative_regulation (decreased) of TLR4 associated with cytokine
8) Confidence 0.42 Published 2007 Journal BMC Physiol Section Body Doc Link PMC1933437 Disease Relevance 0.48 Pain Relevance 0.27
Only myocardial IL-6 protein expression was significantly decreased in TLR4-deficient mice compared to WT after MI/R.
Negative_regulation (decreased) of TLR4
9) Confidence 0.42 Published 2007 Journal BMC Physiol Section Body Doc Link PMC1933437 Disease Relevance 0.36 Pain Relevance 0.21
The ratio between the copy numbers of TLR2, TLR4 and GAPDH represented the normalized TLR2 and TLR4 levels for each sample and could be compared with those of other samples.
Negative_regulation (numbers) of TLR4
10) Confidence 0.41 Published 2008 Journal Clinical Science (London, England : 1979) Section Body Doc Link PMC2552974 Disease Relevance 0 Pain Relevance 0
Inactivation of toll-like receptor 4 signaling promotes survival of retinal neurons following ischemic injury
Negative_regulation (Inactivation) of toll-like receptor 4 in neurons associated with injury
11) Confidence 0.41 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2956702 Disease Relevance 0.63 Pain Relevance 0.12
The mice that lacked Tlr4 showed significantly increased survival of neurons in the ganglion cell layer following ischemic injury, as compared to wild-type controls.


Negative_regulation (lacked) of Tlr4 in ganglion cell layer associated with ganglion cysts and injury
12) Confidence 0.41 Published 2010 Journal Molecular Vision Section Abstract Doc Link PMC2956702 Disease Relevance 1.05 Pain Relevance 0.26
We observed that treatment with the PS-341 significantly decreased Pa-LPS induced IL1-?
Negative_regulation (decreased) of Pa-LPS associated with pseudomonas infection
13) Confidence 0.39 Published 2010 Journal J Nanobiotechnology Section Body Doc Link PMC2954907 Disease Relevance 0.61 Pain Relevance 0.17
as well as suppressing LPS induced endotoxic shock in mice.
Negative_regulation (suppressing) of LPS associated with bacterial infection
14) Confidence 0.38 Published 1999 Journal Met Based Drugs Section Abstract Doc Link PMC2365189 Disease Relevance 0.37 Pain Relevance 0.19
Taken together with the abolition of LPS effect in TLR4 mutant mice, we conclude that commensal microflora induce host defense and decrease bacterial translocation in burn mice through toll-like receptor 4.



Negative_regulation (decrease) of toll-like receptor 4 associated with burns
15) Confidence 0.37 Published 2010 Journal J Biomed Sci Section Abstract Doc Link PMC2901327 Disease Relevance 0.97 Pain Relevance 0.05
They demonstrated a dose dependent decrease of TLR4 mRNA and protein expression in CD14+ human monocytes incubated in vitro with simvastatin or atorvastatin.
Negative_regulation (decrease) of TLR4 mRNA in monocytes
16) Confidence 0.37 Published 2010 Journal Mediators of Inflammation Section Body Doc Link PMC2855078 Disease Relevance 0.31 Pain Relevance 0.58
In TRIFmut mice, S-LPS- or R-LPS-induced BALF TNF levels were also strongly reduced (P<0.001), but PMN influx and BALF LIX levels were not or modestly lowered (Fig. 1A–F).
Negative_regulation (reduced) of LPS
17) Confidence 0.37 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2855719 Disease Relevance 0.13 Pain Relevance 0.23
Macrophages lacking CD14 secreted equal amounts of TNF as macrophages expressing CD14 upon stimulation with R-LPS, but failed to secrete TNF in response to S-LPS which was reversed by addition of sCD14 [14].
Negative_regulation (reversed) of LPS in Macrophages
18) Confidence 0.37 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2855719 Disease Relevance 0.37 Pain Relevance 0.10
In TRIFmut mice, S-LPS- or R-LPS-induced BALF TNF levels were also strongly reduced (P<0.001), but PMN influx and BALF LIX levels were not or modestly lowered (Fig. 1A–F).
Negative_regulation (reduced) of LPS
19) Confidence 0.37 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2855719 Disease Relevance 0.13 Pain Relevance 0.22
Importantly, sCD14 treatment partially reversed the phenotype of CD14KO mice at both S-LPS doses.
Negative_regulation (reversed) of LPS
20) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2855719 Disease Relevance 0.18 Pain Relevance 0.09

General Comments

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