INT145767

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Context Info
Confidence 0.43
First Reported 2005
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 18
Total Number 18
Disease Relevance 11.03
Pain Relevance 5.25

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
MD2 1
alveolar macrophages 1
brains 1
epithelial cells 1
endometrium 1
TLR4 (Homo sapiens)
Pain Link Frequency Relevance Heat
MU agonist 1 99.60 Very High Very High Very High
ischemia 15 99.52 Very High Very High Very High
endometriosis 63 99.38 Very High Very High Very High
medulla 3 99.14 Very High Very High Very High
rheumatoid arthritis 97 98.80 Very High Very High Very High
glial activation 7 98.60 Very High Very High Very High
Inflammation 246 97.76 Very High Very High Very High
cytokine 161 97.68 Very High Very High Very High
analgesia 5 97.40 Very High Very High Very High
Morphine 2 97.00 Very High Very High Very High
Disease Link Frequency Relevance Heat
Disease 203 99.68 Very High Very High Very High
Stomach Cancer 4 99.68 Very High Very High Very High
Cv Unclassified Under Development 16 99.52 Very High Very High Very High
Endometriosis (extended) 114 99.38 Very High Very High Very High
Reperfusion Injury 16 99.16 Very High Very High Very High
Infection 36 98.88 Very High Very High Very High
Rheumatoid Arthritis 200 98.80 Very High Very High Very High
Ulcers 5 98.48 Very High Very High Very High
Osteoarthritis 36 98.32 Very High Very High Very High
Acute Coronary Syndrome 3 97.92 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
We herein report a chemical biology approach by using a rationally designed peptide inhibitor to disrupt the TLR4-MD2 association, thereby blocking TLR4 signaling.
Negative_regulation (blocking) of TLR4 in MD2
1) Confidence 0.43 Published 2009 Journal Chembiochem Section Abstract Doc Link 19184989 Disease Relevance 0.28 Pain Relevance 0.26
In endometriosis, we can observe a significant decrease in TLR3 and TLR4 mRNA levels in eutopic tissues collected during the proliferative phase, when compared to controls (P < 0.05; figure 3A–B).
Negative_regulation (decrease) of TLR4 mRNA associated with endometriosis
2) Confidence 0.41 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.32 Pain Relevance 0.08
of TLR4 mRNA was significantly decreased
Negative_regulation (decreased) of TLR4
3) Confidence 0.41 Published 2008 Journal Mediators of Inflammation Section Body Doc Link PMC2435281 Disease Relevance 0.61 Pain Relevance 0.33
In both conditions, TLR3 and TLR4 were significantly decreased in diseased endometrium when compared to age matched controls.
Negative_regulation (decreased) of TLR4 in endometrium
4) Confidence 0.41 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 1.17 Pain Relevance 0.18
A metaanalysis of published TLR4 and CD14 studies was performed.
Negative_regulation (published) of TLR4
5) Confidence 0.40 Published 2008 Journal J. Rheumatol. Section Body Doc Link 18634146 Disease Relevance 0.09 Pain Relevance 0
TLR4 SNPs reduce the risk of early acute allograft rejection.
Negative_regulation (reduce) of TLR4
6) Confidence 0.40 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 1.90 Pain Relevance 0.42
Opioid agonists were found to also possess TLR4 agonistic activity, predictive of glial activation.
Negative_regulation (possess) of TLR4 associated with mu agonist and glial activation
7) Confidence 0.38 Published 2007 Journal ScientificWorldJournal Section Abstract Doc Link 17982582 Disease Relevance 0.45 Pain Relevance 2.56
Nevertheless, despite the low expression levels of TLR4 in alveolar macrophages, these cells produced significantly higher (p < 0.05) amounts of IL-1?
Negative_regulation (levels) of TLR4 in alveolar macrophages
8) Confidence 0.36 Published 2010 Journal Respir Res Section Body Doc Link PMC2817655 Disease Relevance 0.05 Pain Relevance 0.04
TLR4, which interacts with LPS-bound CD14, is constitutively expressed in circumventricular organs but also in the hypothalamus and medulla; in contrast to CD14, however, there is a downregulation of TLR4 mRNA in the brains of rats challenged by LPS [59].
Negative_regulation (downregulation) of TLR4 in brains associated with medulla
9) Confidence 0.35 Published 2005 Journal Crit Care Section Body Doc Link PMC1065096 Disease Relevance 0.24 Pain Relevance 0.08
The out-degree distribution gives rise to three protein hubs, namely IL6 and TLR2 and TLR4 (the number of hubs is reduced here due to the higher power-law exponent), with out-degree greater than 2.
Negative_regulation (reduced) of TLR4
10) Confidence 0.32 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2855702 Disease Relevance 0 Pain Relevance 0.03
Abnormal expression of TLR4 can predispose to defective HO-1 expression in BD PBMCs, because TLR4 may be a putative HO-1 repressor in hepatic ischemia/reperfusion injury mouse model [35].
Negative_regulation (repressor) of TLR4 associated with reperfusion injury, ischemia and disease
11) Confidence 0.31 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2374472 Disease Relevance 1.54 Pain Relevance 0.11
The data suggest that activation signals through essentially over-expressed TLR4 cause reduction in HO-1 expression in peripheral blood mononuclear cells (PBMC), resulting in an augmentation of inflammatory responses in BD.


Negative_regulation (reduction) of TLR4 in mononuclear cells associated with inflammatory response and disease
12) Confidence 0.31 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2374472 Disease Relevance 1.58 Pain Relevance 0.39
TLR2 protein was suppressed by 19 ± 7% below baseline at 4 h following insulin infusion (P < 0.05) when compared with baseline and to control subjects (Fig. 2), while TLR4 protein levels were reduced by only 8 ± 5% (P = NS).
Negative_regulation (reduced) of TLR4
13) Confidence 0.28 Published 2008 Journal Diabetes Care Section Body Doc Link PMC2518353 Disease Relevance 0.08 Pain Relevance 0
CD14 was reduced from 10.6 ± 16.6% before treatment to 2.5 ± 2% after treatment (P = 0.011), TLR4 was reduced from 46.9 ± 32.7% to 11.7 ± 12.5% (P = 0.008) and TLR2 was reduced from 11.7 ± 19.4% to 1.8 ± 2.9% (P = 0.012).


Negative_regulation (reduced) of TLR4
14) Confidence 0.24 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1297589 Disease Relevance 0.27 Pain Relevance 0.18
Furthermore, 2 hours after PCI a significant decrease in TLR2 and TLR4 response (p<0.001) and TLR2 and TLR4 expression (p = 0.001 and p = 0.068, respectively) was seen.
Negative_regulation (decrease) of TLR4
15) Confidence 0.23 Published 2008 Journal Heart Section Body Doc Link 17686802 Disease Relevance 0.12 Pain Relevance 0
The absence of a clear suppression of TLR4 protein level may be due to the relatively short period of infusion.
Negative_regulation (suppression) of TLR4
16) Confidence 0.20 Published 2008 Journal Diabetes Care Section Body Doc Link PMC2518353 Disease Relevance 0.09 Pain Relevance 0.05
The suppressive effect of insulin on TLR4 is also important in understanding the relationship of inflammation to obesity and insulin resistance and atherosclerosis.



Negative_regulation (suppressive) of TLR4 associated with inflammation, atherosclerosis, obesity and insulin resistance
17) Confidence 0.20 Published 2008 Journal Diabetes Care Section Body Doc Link PMC2518353 Disease Relevance 1.57 Pain Relevance 0.20
Interestingly, Th2 cytokines were shown to play an important role in balancing TLR signalling in human intestinal epithelial cells by mediating downregulation of TLR3 and TLR4 expression and function [42].
Negative_regulation (downregulation) of TLR4 in epithelial cells associated with cytokine
18) Confidence 0.18 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.67 Pain Relevance 0.34

General Comments

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