INT182124

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Context Info
Confidence 0.10
First Reported 2005
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 14
Total Number 21
Disease Relevance 16.11
Pain Relevance 4.65

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

cytoplasm (IRF6, TLR4) cytosol (IRF6) signal transduction (TLR4)
plasma membrane (TLR4) intracellular (TLR4) nucleus (IRF6)
Anatomy Link Frequency
liver 2
MD2 2
T cells 2
plasma 1
brains 1
IRF6 (Homo sapiens)
TLR4 (Homo sapiens)
Pain Link Frequency Relevance Heat
agonist 432 100.00 Very High Very High Very High
Bile 40 99.36 Very High Very High Very High
rheumatoid arthritis 138 99.04 Very High Very High Very High
cytokine 434 98.72 Very High Very High Very High
Inflammation 620 98.52 Very High Very High Very High
tolerance 65 98.28 Very High Very High Very High
spinal inflammation 155 97.72 Very High Very High Very High
alcohol 32 96.88 Very High Very High Very High
Arthritis 91 96.12 Very High Very High Very High
medulla 3 95.92 Very High Very High Very High
Disease Link Frequency Relevance Heat
Sprains And Strains 15 99.92 Very High Very High Very High
Chronic Hepatitis 16 99.48 Very High Very High Very High
Disease 343 99.34 Very High Very High Very High
Rheumatoid Arthritis 138 99.04 Very High Very High Very High
INFLAMMATION 794 98.52 Very High Very High Very High
Shock 39 98.52 Very High Very High Very High
Cirrhosis 488 98.08 Very High Very High Very High
Low Back Pain 155 97.72 Very High Very High Very High
Lung Injury 6 97.28 Very High Very High Very High
Cancer 53 96.96 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The binding and activation of LPS to TLR4 needs three additional components: MD2, a membrane protein whose association with TLR4 is required for the binding of LPS [5]; LPS-binding protein (LBP), which extracts LPS monomers from the aggregated form [6,7]; and CD14, which transfers LPS to the TLR4/MD2 transmembrane co-receptor, which then triggers the downstream molecular events [2].
LPS Binding (binding) of TLR4 in MD2
1) Confidence 0.10 Published 2007 Journal Molecular Vision Section Body Doc Link PMC2768757 Disease Relevance 0.12 Pain Relevance 0.08
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].
LPS Binding (interacts) of TLR4 in brains associated with medulla
2) Confidence 0.09 Published 2005 Journal Crit Care Section Body Doc Link PMC1065096 Disease Relevance 0.37 Pain Relevance 0.08
A cell wall component, peptidoglycan (PGN) of gram-positive bacteria is the preferred ligand of the TLR2 homodimer, and lipopolysaccharides (LPS) of gram-negative bacteria is recognized by TLR4 [4].
LPS Binding (recognized) of TLR4
3) Confidence 0.08 Published 2007 Journal Molecular Vision Section Body Doc Link PMC2768757 Disease Relevance 0.12 Pain Relevance 0.09
TLR2 and TLR4 recognize lipoproteins and lipopolysaccharide (LPS), respectively.
LPS Binding (recognize) of TLR4
4) Confidence 0.07 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2374472 Disease Relevance 1.64 Pain Relevance 0.21
Moreover, elevated soluble CD14 in plasma of BD patients may further facilitate LPS binding to TLR4 [36].
LPS Binding (binding) of TLR4 in plasma associated with disease
5) Confidence 0.06 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2374472 Disease Relevance 1.57 Pain Relevance 0.11
Binding of LPS to CD14/TLR4 on KCs activates production of cytokines and oxidants, primary mediators of early ethanol-induced liver injury.
LPS Binding (Binding) of TLR4 in liver associated with injury, agonist and cytokine
6) Confidence 0.06 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 1.10 Pain Relevance 0.50
LPS and endogenous TLR4 ligands are increased in the serum and livers of patients with liver cirrhosis and of animals with experimental chronic liver disease.
LPS Binding (ligands) of TLR4 in liver associated with liver disease, cirrhosis and agonist
7) Confidence 0.05 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 1.90 Pain Relevance 0.63
The uptake of LPS by hepatocytes in vivo is through a CD14-TLR4-MD2-dependent mechanism, and is mediated by ?
LPS Binding (mechanism) of TLR4 in MD2 associated with agonist
8) Confidence 0.05 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 1.03 Pain Relevance 0.40
Because LPS (a TLR4 ligand) has been shown to suppress interleukin-10-dependent HO-1 expression in human PBMCs [29], it is plausible that excessively expressed TLR4 contributes to defective HO-1 expression in PBMCs from BD patients.
LPS Binding (ligand) of TLR4 associated with disease
9) Confidence 0.05 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2374472 Disease Relevance 0.70 Pain Relevance 0.05
Whole gram-negative bacteria are recognized not only through TLR4 (by LPS) but also TLR 2 (by bacterial lipopeptides).
LPS Binding (recognized) of TLR4
10) Confidence 0.05 Published 2005 Journal Respir Res Section Body Doc Link PMC1187924 Disease Relevance 0.79 Pain Relevance 0.05
These TLR4 SNPs are primarily associated with a blunted response to inhaled LPS in humans [126].
LPS Binding (associated) of TLR4 associated with agonist
11) Confidence 0.05 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 1.67 Pain Relevance 0.47
Upon LPS recognition, TLR4 undergoes oligomerization and recruits its downstream adaptors through interactions with the TIR domains.
LPS Binding (recognition) of TLR4
12) Confidence 0.05 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 0 Pain Relevance 0
For example, for the initiation of LPS to activate intracellular TLR4 signaling, the ligand first interacts with circulating LPS-binding protein (LBP) along with three LRR domain-containing proteins, TLR4 and the two co-receptors CD14 and myeloid differentiation protein (MD)2, together comprising the LPS receptor complex [5].
LPS Binding (interacts) of TLR4
13) Confidence 0.05 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 0.40 Pain Relevance 0.07
Besides its natural exogenous substrate LPS, there are endogenous substrates for TLR4 that also bind and activate TLR4 [43], including low molecular weight hyaluronic acid [44,45], free fatty acids (FFAs) [46], fibrinogen [47], fibronectin [48], heat shock proteins (HSPs) 60 and 70 [49,50] and high mobility group box (HMGB)1 [51].
LPS Binding (bind) of TLR4 associated with shock
14) Confidence 0.05 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 0.78 Pain Relevance 0.05
Direct engagement of TLR4 by LPS on Tregs upregulates several activation markers, and induces Treg proliferation or survival without the need for TCR ligation.
LPS Binding (engagement) of TLR4 associated with agonist
15) Confidence 0.05 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 0.65 Pain Relevance 0.27
LPS binding protein, another TLR-related molecule, is also known to support binding of LPS to TLR4.
LPS Binding (binding) of TLR4
16) Confidence 0.04 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1297589 Disease Relevance 0.58 Pain Relevance 0.38
TLR4 binds LPS and thus provides activating signals to the CD4+CD28null T cells, which can be reversed with TLR4 blocking antibodies (Figure 5c).
LPS Binding (binds) of TLR4 in T cells
17) Confidence 0.04 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1297589 Disease Relevance 0.34 Pain Relevance 0.16
LPS binding protein, another TLR-related molecule, is also known to support binding of LPS to TLR4.
LPS Binding (binding) of TLR4
18) Confidence 0.03 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1297589 Disease Relevance 0.59 Pain Relevance 0.38
LPS binding to TLR4 is promoted by CD14, which can be present either in a membrane-bound form (mCD14) or a soluble form (sCD14) [6,7].
LPS Binding (binding) of TLR4
19) Confidence 0.03 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1297589 Disease Relevance 0.09 Pain Relevance 0.08
TLR-4, the main receptor for LPS recognition, was significantly expressed on CD4+CD28null T cells in AS (23.1 ± 21.9% versus 0.9 ± 1.2%), in PsA (12.4 ± 18.1% versus 0.4 ± 0.5%) and in RA (23.1 ± 24.7% versus 0.6 ± 0.9%; each with P < 0.001).
LPS Binding (recognition) of TLR-4 in T cells associated with spinal inflammation, rheumatoid arthritis and arthritis
20) Confidence 0.03 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1297589 Disease Relevance 0.88 Pain Relevance 0.53

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