INT134651

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Context Info
Confidence 0.48
First Reported 2005
Last Reported 2011
Negated 2
Speculated 5
Reported most in Body
Documents 89
Total Number 94
Disease Relevance 66.96
Pain Relevance 23.19

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 4
liver 4
MD2 4
epithelial cells 3
T cells 3
TLR4 (Homo sapiens)
TLR4 - D299G (1)
Pain Link Frequency Relevance Heat
agonist 1021 100.00 Very High Very High Very High
spinal inflammation 103 100.00 Very High Very High Very High
cINOD 36 100.00 Very High Very High Very High
Inflammation 2558 99.96 Very High Very High Very High
cytokine 1433 99.90 Very High Very High Very High
Opioid 112 99.84 Very High Very High Very High
antagonist 70 99.84 Very High Very High Very High
Arthritis 480 99.80 Very High Very High Very High
Inflammatory response 441 99.24 Very High Very High Very High
fibrosis 380 99.20 Very High Very High Very High
Disease Link Frequency Relevance Heat
Death 167 100.00 Very High Very High Very High
Osteoarthritis 106 100.00 Very High Very High Very High
Low Back Pain 105 100.00 Very High Very High Very High
Shock 71 100.00 Very High Very High Very High
Neonatal Necrotizing Enterocolitis 68 100.00 Very High Very High Very High
INFLAMMATION 3008 99.96 Very High Very High Very High
Injury 766 99.96 Very High Very High Very High
Sprains And Strains 95 99.92 Very High Very High Very High
Chronic Disease 56 99.92 Very High Very High Very High
Communicable Diseases 40 99.92 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Innate immune responses to Gram-negative bacteria involve in a central role the binding of lipopolysaccharide to TLR4.
TLR4 Binding (binding) of
1) Confidence 0.48 Published 2008 Journal Rheumatol. Int. Section Abstract Doc Link 18034244 Disease Relevance 0.95 Pain Relevance 0.68
We herein report a chemical biology approach by using a rationally designed peptide inhibitor to disrupt the TLR4-MD2 association, thereby blocking TLR4 signaling.
TLR4 Binding (association) of in MD2
2) Confidence 0.48 Published 2009 Journal Chembiochem Section Abstract Doc Link 19184989 Disease Relevance 0.28 Pain Relevance 0.27
CONCLUSION: Given the functional role of TLR4 variants in the innate immune system, larger studies are now warranted to elucidate the association of TLR4 variants in AS.


TLR4 Binding (association) of in immune system
3) Confidence 0.48 Published 2007 Journal J. Rheumatol. Section Body Doc Link 17143969 Disease Relevance 0.07 Pain Relevance 0
The mechanism of immunosuppression of HSP10 is less well defined but is believed to inhibit intracellular signaling pathways stimulated by ligand interaction with selected Toll-like receptors (TLRs) [17].
Toll Binding (interaction) of
4) Confidence 0.47 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2065903 Disease Relevance 0.59 Pain Relevance 0.18
The authors speculate that the structure could potentially bind Toll-like receptors (TLRs) or other pathogen associated molecular pattern (PAMP) binding molecules.
Toll Binding (bind) of
5) Confidence 0.47 Published 2010 Journal Parasit Vectors Section Body Doc Link PMC2993695 Disease Relevance 0 Pain Relevance 0.07
Since repair processes occur every month in the uterus of premenopausal women, we believe that the interaction between hyaluronan and TLR4 might promote the endometrial repair.
TLR4 Spec (might) Binding (interaction) of in uterus
6) Confidence 0.46 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.44 Pain Relevance 0.13
Hyaluronan is released by necrotic cells, interacts with TLR4 and activates CD44 mediated signalling [38].
TLR4 Binding (interacts) of
7) Confidence 0.46 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.45 Pain Relevance 0.14
In agreement with Pioli et al., who detected TLR4, CD14 and MyD88 transcripts in human endometrium [14], we were able to co-localize TLR4 with CD14 proteins suggesting the presence of both interacting receptors CD14 and TLR4 in the endometrial cells.
TLR4 Binding (interacting) of in endometrium
8) Confidence 0.46 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.31 Pain Relevance 0.08
Recent studies have uncovered an important role for TLR4 signaling in liver fibrogenesis and the association of TLR4 polymorphisms with fibrosis risk.
TLR4 Binding (association) of in liver associated with fibrosis and cirrhosis
9) Confidence 0.45 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 1.22 Pain Relevance 0.12
TLR4 also recognizes proteins from respiratory syncytial virus, vesicular stomatitis virus and mouse mammary tumor virus [40-42].


TLR4 Binding (recognizes) of in respiratory associated with cancer, vesicular stomatitis and respiratory syncytial virus
10) Confidence 0.45 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 0.78 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].
TLR4 Binding (recognized) of
11) Confidence 0.43 Published 2007 Journal Molecular Vision Section Body Doc Link PMC2768757 Disease Relevance 0.12 Pain Relevance 0.09
Many studies report the association between these TLR4 genetic polymorphisms and disease risk.
TLR4 Binding (association) of associated with disease
12) Confidence 0.39 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 1.76 Pain Relevance 0.48
Two commonly occurring SNPs in the human TLR4 gene (Asp299Gly and Thr399Ile) have been shown to be associated with increased risk of Gram-negative bacteremia in sepsis patients and with susceptibility to inflammatory bowel disease.
TLR4 gene (D299G) Binding (associated) of in bowel associated with inflammation, bacteremia and sepsis
13) Confidence 0.37 Published 2008 Journal Rheumatol. Int. Section Abstract Doc Link 18034244 Disease Relevance 1.00 Pain Relevance 0.71
Association of toll-like receptor 4 variants and ankylosing spondylitis: a case-control study.
toll-like receptor 4 Binding (Association) of associated with spinal inflammation
14) Confidence 0.37 Published 2007 Journal J. Rheumatol. Section Title Doc Link 17143969 Disease Relevance 0.10 Pain Relevance 0.22
We did not find any association for TLR4 Asp299Gly*2 and TLR4 Thr399Ile*2 hyporeactive alleles.


TLR4 Neg (not) Binding (association) of
15) Confidence 0.36 Published 2007 Journal BMC Cancer Section Body Doc Link PMC1868033 Disease Relevance 0.91 Pain Relevance 0
TLR4 was also found to be associated with the response to rituximab, which is used in the treatment of many lymphomas, leukemias, and some autoimmune disorders [36].
TLR4 Binding (associated) of associated with leukemia, autoimmune disease and lymphatic system cancer
16) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2855702 Disease Relevance 1.57 Pain Relevance 0.34
Second, both caspase-independent cell death and apoptosis, particularly when related to the engagement of death receptors (DRs) or Toll-like receptors (TLR) by their respective ligands, critically involves the kinase RIP (Receptor interacting protein), which is currently seen as one of the crucial, and redox sensitive, cellular crossroads determining whether cells live or die (Figure 22).
Toll Binding (engagement) of associated with apoptosis and death
17) Confidence 0.36 Published 2008 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2584013 Disease Relevance 1.04 Pain Relevance 0.03
Pathogens are recognized by Toll-like receptors on epithelial cells, which induce the release of several pro-inflammatory cytokines (Hewson et al 2005; Ritter et al 2005).
Toll Binding (recognized) of in epithelial cells associated with inflammation and cytokine
18) Confidence 0.36 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2629961 Disease Relevance 1.35 Pain Relevance 0.21
B activation, such as pro-inflammatory cytokines and ligation of Toll-like receptors, but triggering of highly specialized antigen receptors such as the T-cell receptor is also dependent on this pathway [12].
Toll Binding (ligation) of in T-cell associated with inflammation and cytokine
19) Confidence 0.36 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1779420 Disease Relevance 0.79 Pain Relevance 0.30
Additionally, they can interact with other pattern recognition receptors such as Toll-like receptors.
Toll Binding (interact) of
20) Confidence 0.36 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2592801 Disease Relevance 0.77 Pain Relevance 0

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