INT118742

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Context Info
Confidence 0.69
First Reported 2004
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 32
Total Number 32
Disease Relevance 27.55
Pain Relevance 11.09

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
spinal cord 2
adipose tissue 2
plasma 1
spinal 1
spinal nerve 1
Tlr4 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
Eae 80 99.68 Very High Very High Very High
Spinal cord 73 99.68 Very High Very High Very High
cytokine 410 99.62 Very High Very High Very High
Cancer pain 250 99.48 Very High Very High Very High
intrathecal 78 98.90 Very High Very High Very High
antagonist 26 98.84 Very High Very High Very High
tolerance 85 97.92 Very High Very High Very High
Inflammation 669 97.56 Very High Very High Very High
Inflammatory mediators 59 97.20 Very High Very High Very High
Pain 112 96.40 Very High Very High Very High
Disease Link Frequency Relevance Heat
Targeted Disruption 15 100.00 Very High Very High Very High
Sepsis 882 99.98 Very High Very High Very High
Bone Cancer 270 99.68 Very High Very High Very High
Injury 121 99.68 Very High Very High Very High
Apoptosis 48 99.42 Very High Very High Very High
Hypersensitivity 91 99.36 Very High Very High Very High
Obesity 440 99.32 Very High Very High Very High
Infection 69 99.04 Very High Very High Very High
Nervous System Injury 111 99.00 Very High Very High Very High
Death 45 98.96 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
in spinal cord tissues was significantly lower in the CCI group during the course of TLR4-siRNA treatment, indicating that intrathecal administration of TLR4-siRNA significantly attenuated TLR4 induction in the CCI rats (Figure 3).


Positive_regulation (induction) of TLR4 in spinal cord associated with eae, intrathecal and spinal cord
1) Confidence 0.69 Published 2010 Journal International Journal of Medical Sciences Section Body Doc Link PMC2920570 Disease Relevance 1.41 Pain Relevance 1.38
We and others have previously demonstrated that TLR4 signaling is activated in diet induced obesity (DIO), and that this activation culminates in an increase in the activation of downstream effectors such as IKK?
Positive_regulation (activated) of TLR4 associated with obesity
2) Confidence 0.61 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2997789 Disease Relevance 1.02 Pain Relevance 0.11
Sepsis induced an increase in the expression/activation of TLR4 and its downstream signaling JNK and IKK/NF-?
Positive_regulation (activation) of TLR4 associated with sepsis
3) Confidence 0.61 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2997789 Disease Relevance 0.71 Pain Relevance 0.20
TLR4 expression increases in the bone cancer pain model
Positive_regulation (increases) of TLR4 associated with cancer pain and bone cancer
4) Confidence 0.50 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 1.22 Pain Relevance 0.58
Tanga et al. demonstrated that sensory neuron damage leads to the release of such substances and that these stimulate microglial TLR4 in the spinal cord, initiating microglial activation [11].
Positive_regulation (stimulate) of TLR4 in spinal cord associated with spinal cord
5) Confidence 0.50 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 0.85 Pain Relevance 1.08
Tibia tumor-induced cancer pain involves spinal p38 mitogen-activated protein kinase activation via TLR4-dependent mechanisms.
Positive_regulation (activation) of TLR4 in spinal associated with cancer pain and cancer
6) Confidence 0.48 Published 2010 Journal Brain Res. Section Title Doc Link 20478276 Disease Relevance 1.06 Pain Relevance 0.89
The activation of TLR4 triggers two major downstream signaling cascades, the NF-kB and mitogen-activated protein kinase (MAPK) transduction cascades 36.
Positive_regulation (activation) of TLR4
7) Confidence 0.47 Published 2010 Journal International Journal of Medical Sciences Section Body Doc Link PMC2920570 Disease Relevance 0.66 Pain Relevance 0.36
These data shed light on the mechanistic link between microglial TLR4 activation and behavioral hypersensitivity.
Positive_regulation (activation) of TLR4 associated with hypersensitivity
8) Confidence 0.46 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 1.68 Pain Relevance 0.88
At the protein level, data from several western blot experiments revealed a significant up-regulation of TLR4(n = 4, ANOVA1w, P < 0.01, post hoc Dunnett testing) on the sixth day after inoculation (Fig. 2A, C).
Positive_regulation (regulation) of TLR4
9) Confidence 0.46 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 0.98 Pain Relevance 0.45
Overall, our data demonstrate that atorvastatin exerts direct regulatory effects on TLR4 expression/activation in an animal model of sepsis that influences TLR4 signaling.
Positive_regulation (activation) of TLR4 associated with sepsis
10) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2997789 Disease Relevance 1.15 Pain Relevance 0.07
Our data show that atorvastatin decreases TLR4 expression/activation, a modulation that might have a role in the attenuated expression of inflammatory mediators in response to a septic insult.
Positive_regulation (activation) of TLR4 associated with inflammatory mediators
11) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2997789 Disease Relevance 0.70 Pain Relevance 0.11
The reduction in TLR4 expression/activation, observed in our study, is in accordance with a previous study that also observed this effect on TLR4 expression/activation with different statins and cell types [51].
Positive_regulation (activation) of TLR4
12) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2997789 Disease Relevance 0.65 Pain Relevance 0.14
Overall, our data demonstrate that atorvastatin exerts direct regulatory effects on TLR4 expression/activation in an animal model of sepsis that influences TLR4 signaling.
Positive_regulation (influences) of TLR4 associated with sepsis
13) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2997789 Disease Relevance 1.19 Pain Relevance 0.07
Activation of TLR4 on microglial cells may lead to astroglial activation [77].
Positive_regulation (Activation) of TLR4 in microglial cells
14) Confidence 0.42 Published 2009 Journal Mol Pain Section Body Doc Link PMC2806354 Disease Relevance 0.92 Pain Relevance 0.84
The endotoxemia that occurs after strenuous exercise results in increased circulating LPS and may be another mechanism underlying the elevation in TLR-4 and NF-kBp65 protein expression [21].
Positive_regulation (elevation) of TLR-4 associated with endotoxemia
15) Confidence 0.42 Published 2010 Journal Lipids Health Dis Section Body Doc Link PMC2959201 Disease Relevance 0.50 Pain Relevance 0.12
Our results show that there is a increase in TLR-4 and NFkBp65 protein expression in adipose tissue after overload exercise in rats, and which might be associated with higher endotoxin levels.
Positive_regulation (increase) of TLR-4 in adipose tissue associated with obesity
16) Confidence 0.42 Published 2010 Journal Lipids Health Dis Section Body Doc Link PMC2959201 Disease Relevance 0.47 Pain Relevance 0.11
Taken together, our results suggest that the increase in cytokine concentration and augmented TLR-4 and NF-kBp65 protein expression induced by overtraining in the epidydymal adipose tissue may lead to a shift toward increased inflammation.
Positive_regulation (augmented) of TLR-4 in adipose tissue associated with inflammation, obesity and cytokine
17) Confidence 0.42 Published 2010 Journal Lipids Health Dis Section Body Doc Link PMC2959201 Disease Relevance 0.77 Pain Relevance 0.17
Fig. 3 shows that sepsis induced TLR4 protein levels and activation, as demonstrated by an increase in TLR4/MyD88 interaction in the three tissues investigated, and atorvastatin reduced this early step of TLR4 activation and also TLR4 expression (Fig. 3A–C).
Positive_regulation (induced) of TLR4 associated with sepsis
18) Confidence 0.41 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2997789 Disease Relevance 0.88 Pain Relevance 0.20
In animal models of sepsis, there is a down regulation of the PI3K/Akt pathway that may be the consequence of TLR4 activation and downstream in activation of well established inducers of insulin resistance as JNK, IKK-?
Positive_regulation (activation) of TLR4 associated with insulin resistance and sepsis
19) Confidence 0.41 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2997789 Disease Relevance 1.38 Pain Relevance 0.30
Fig. 3 shows that sepsis induced TLR4 protein levels and activation, as demonstrated by an increase in TLR4/MyD88 interaction in the three tissues investigated, and atorvastatin reduced this early step of TLR4 activation and also TLR4 expression (Fig. 3A–C).
Positive_regulation (activation) of TLR4 associated with sepsis
20) Confidence 0.41 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2997789 Disease Relevance 0.86 Pain Relevance 0.20

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