INT168279

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Context Info
Confidence 0.54
First Reported 2009
Last Reported 2010
Negated 3
Speculated 0
Reported most in Body
Documents 17
Total Number 17
Disease Relevance 8.97
Pain Relevance 5.50

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
lung 2
nerve 1
spinal cord 1
Tlr4 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
Pain 98 99.80 Very High Very High Very High
Cancer pain 250 99.64 Very High Very High Very High
Eae 80 99.40 Very High Very High Very High
Inflammation 197 98.32 Very High Very High Very High
intrathecal 77 98.22 Very High Very High Very High
Spinal cord 73 98.04 Very High Very High Very High
cytokine 251 97.80 Very High Very High Very High
Inflammatory response 73 94.80 High High
Neuropathic pain 110 93.16 High High
central sensitization 5 92.72 High High
Disease Link Frequency Relevance Heat
Pain 172 99.80 Very High Very High Very High
Infection 29 99.74 Very High Very High Very High
Cancer Pain 15 99.64 Very High Very High Very High
Apoptosis 3 99.42 Very High Very High Very High
Injury 104 99.40 Very High Very High Very High
Bone Cancer 270 99.20 Very High Very High Very High
INFLAMMATION 270 98.32 Very High Very High Very High
Nervous System Injury 103 98.16 Very High Very High Very High
Lung Injury 91 97.92 Very High Very High Very High
Stress 6 96.56 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
At the protein level, whether in the IBCP group (Fig. 6C, E) or in the WBCP group (Fig. 6D, F), data from several western blot experiments revealed a significant up-regulation of the TLR4 (n = 4, ANOVA1w, P < 0.01, post hoc Dunnett testing) protein in mismatch siRNA- and vehicle-treated bone cancer pain rats relative to that from normal rats.
Regulation (regulation) of TLR4 associated with cancer pain and bone cancer
1) Confidence 0.54 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 0.63 Pain Relevance 0.61
There was no change in TLR-4 among groups.
Neg (no) Regulation (change) of TLR-4
2) Confidence 0.45 Published 2010 Journal Lipids Health Dis Section Body Doc Link PMC2959201 Disease Relevance 0.30 Pain Relevance 0.09
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).
Regulation (regulation) of TLR4
3) Confidence 0.45 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 0.98 Pain Relevance 0.45
In addition to measuring the effect of the siRNA treatment on TLR4 mRNA, we also determined their effect TLR4 protein expression 48 h after transfection, by western blot analysis.
Regulation (effect) of TLR4 mRNA
4) Confidence 0.45 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 0.19 Pain Relevance 0.30
Although our data may imply a role for the TLR4/IRAK-3 system in regulating multiple pro-inflammatory cytokines during MV, we acknowledge some limitations to this study.
Regulation (role) of TLR4 associated with inflammation and cytokine
5) Confidence 0.40 Published 2010 Journal Respir Res Section Body Doc Link PMC2841148 Disease Relevance 0.53 Pain Relevance 0.28
B and up-regulated TLR4 but not TLR2
Neg (not) Regulation (regulated) of TLR4
6) Confidence 0.40 Published 2010 Journal Respir Res Section Body Doc Link PMC2841148 Disease Relevance 0.26 Pain Relevance 0.10
In this study, we have shown that, in non-infected animals, MV for 4 h induced IRAK-3 down-regulation, TLR4 up-regulation and that different patterns of MV caused different patterns of IRAK-3 expression.
Regulation (regulation) of TLR4
7) Confidence 0.40 Published 2010 Journal Respir Res Section Body Doc Link PMC2841148 Disease Relevance 0.32 Pain Relevance 0.23
As shown in Figure 3, mechanically ventilated animals up-regulated TLR4 but not TLR2 protein levels in the lungs.
Neg (not) Regulation (regulated) of TLR4 in lungs
8) Confidence 0.40 Published 2010 Journal Respir Res Section Body Doc Link PMC2841148 Disease Relevance 0.24 Pain Relevance 0.10
We observed that high VT MV for 4 h induced up-regulation of TLR4 (and not TLR2) protein levels, a receptor related to LPS signal transduction and the classical NF-?
Regulation (regulation) of TLR4
9) Confidence 0.40 Published 2010 Journal Respir Res Section Body Doc Link PMC2841148 Disease Relevance 0.32 Pain Relevance 0.12
SiRNAs targeting the cDNA sequence of rat TLR4 (GenBank accession NM_019178) were: 5'-CUACCAACAGAGAGGAUAU-3” (siRNA1), 5'-GUCUCAGAUAUCUAGAUCU-3' (siRNA2), 5'-GAGCCGGAAAGUUAUUGUG-3' (siRNA3).
Regulation (targeting) of TLR4
10) Confidence 0.27 Published 2010 Journal International Journal of Medical Sciences Section Body Doc Link PMC2920570 Disease Relevance 0.36 Pain Relevance 0.42
In addition, we have also demonstrated that suppression of TLR4 with intrathecal siRNA delivery could alleviate pain responses in a rat CCI model, suggesting that siRNA targeting TLR4 could be of practical value in clinical situation.



Regulation (targeting) of TLR4 associated with pain, eae and intrathecal
11) Confidence 0.27 Published 2010 Journal International Journal of Medical Sciences Section Body Doc Link PMC2920570 Disease Relevance 1.38 Pain Relevance 1.12
Four different siRNA duplexes targeting the S-D rat TLR4 were selected using standard siRNA design rules.
Regulation (targeting) of TLR4
12) Confidence 0.27 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 0.60 Pain Relevance 0.12
Our results provide evidence for a role of the key innate immune receptor, TLR4, in a rat model of bone cancer pain.
Regulation (role) of TLR4 associated with cancer pain and bone cancer
13) Confidence 0.27 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 0.35 Pain Relevance 0.35
These results demonstrate that TLR4-dependent phosphorylation of p38MAPK in spinal cord of rats might contribute to the development and maintenance of bone cancer pain, and p38MAPK and TLR4 would possibly be the potential targets for pain therapy.
Regulation (targets) of TLR4 in spinal cord associated with pain, cancer pain and spinal cord
14) Confidence 0.26 Published 2010 Journal Brain Res. Section Abstract Doc Link 20478276 Disease Relevance 0.91 Pain Relevance 0.78
The main findings of this study were the observations that high VT MV, in the absence of infection, induced up-regulation of TLR4 and down-regulation of IRAK3 and I?
Regulation (regulation) of TLR4 associated with infection
15) Confidence 0.24 Published 2010 Journal Respir Res Section Body Doc Link PMC2841148 Disease Relevance 0.38 Pain Relevance 0.15
Mechanical ventilation modulates TLR4 and IRAK-3 in a non-infectious, ventilator-induced lung injury model

Background

Regulation (modulates) of TLR4 in lung associated with lung injury
16) Confidence 0.24 Published 2010 Journal Respir Res Section Title Doc Link PMC2841148 Disease Relevance 0.30 Pain Relevance 0
Caspase 3, known to be involved in apoptosis [65] and cell loss [66] and TLR4 modulation [67] are upregulated in both adult and young SNI group, which is consistent with the stress produced by the nerve injury. cAMP responsive element modulator (CREM) isoform (ICER) has a demonstrated role in c-fos regulation after thermal stimulation and its overexpression represses the c-fos and c-jun promoters and attenuates early gene induction following noxious stimulation [68].
Regulation (modulation) of TLR4 in nerve associated with stress, nervous system injury and apoptosis
17) Confidence 0.19 Published 2009 Journal Mol Pain Section Body Doc Link PMC2799401 Disease Relevance 0.92 Pain Relevance 0.30

General Comments

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