INT117220

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Context Info
Confidence 0.69
First Reported 2003
Last Reported 2010
Negated 1
Speculated 2
Reported most in Body
Documents 64
Total Number 81
Disease Relevance 53.61
Pain Relevance 17.33

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
liver 5
T cells 4
intestinal epithelium 2
monocytes 2
macrophage 1
TLR4 (Homo sapiens)
TLR4 - D299G (1)
Pain Link Frequency Relevance Heat
agonist 965 100.00 Very High Very High Very High
Angina 13 100.00 Very High Very High Very High
alcohol 74 99.98 Very High Very High Very High
Inflammation 2027 99.84 Very High Very High Very High
rheumatoid arthritis 388 99.78 Very High Very High Very High
cytokine 1275 99.60 Very High Very High Very High
Arthritis 356 99.40 Very High Very High Very High
Opioid 67 99.36 Very High Very High Very High
Inflammatory response 411 98.72 Very High Very High Very High
spinal inflammation 143 98.24 Very High Very High Very High
Disease Link Frequency Relevance Heat
Stable Angina Pectoris 3 100.00 Very High Very High Very High
Pancreatitis 5 99.96 Very High Very High Very High
Disease 903 99.86 Very High Very High Very High
Inflammatory Bowel Disease 44 99.84 Very High Very High Very High
Cv General 3 Under Development 13 99.84 Very High Very High Very High
Obesity 405 99.80 Very High Very High Very High
Rheumatoid Arthritis 594 99.78 Very High Very High Very High
Injury 697 99.74 Very High Very High Very High
Systemic Lupus Erythematosus 44 99.66 Very High Very High Very High
Infection 287 99.60 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Moreover, TLR4 expression levels in stable angina pectoris (SAP) patients were elevated compared with those in non-CAD subjects (P < 0.05), and those in acute coronary syndrome patients were higher than SAP patients even in low-hsCRP subjects (P < 0.01).
Positive_regulation (elevated) of TLR4 associated with stable angina pectoris, acute coronary syndrome, angina and coronary artery disease
1) Confidence 0.69 Published 2006 Journal Life Sci. Section Abstract Doc Link 17045300 Disease Relevance 1.60 Pain Relevance 0.30
Subsequent studies have shown that APCs need activation signals to provide co-stimulatory ligands, for example through the activation of Toll-like receptors [4,5].
Positive_regulation (activation) of Toll
2) Confidence 0.67 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2582810 Disease Relevance 0.06 Pain Relevance 0
DAMP activation of Toll-like receptors (TLRs) induces inflammatory gene expression to mediate tissue repair.
Positive_regulation (activation) of Toll associated with inflammation
3) Confidence 0.67 Published 2010 Journal Mediators of Inflammation Section Abstract Doc Link PMC2913853 Disease Relevance 0.96 Pain Relevance 0.28
The current preparation includes a glutaraldehyde-modified antigen absorbed onto L-tyrosine depot to enhance tolerability plus MPL to improve efficacy via activation of toll-4 receptors.
Positive_regulation (activation) of toll
4) Confidence 0.67 Published 2010 Journal Allergy, Asthma & Immunology Research Section Body Doc Link PMC2946700 Disease Relevance 0.86 Pain Relevance 0.04
Toll-like receptors (TLR) recognize microbial components and are also activated by endogenous molecules possibly implicated in autoimmune arthritis.
Positive_regulation (activated) of Toll associated with arthritis
5) Confidence 0.67 Published 2006 Journal Lab. Invest. Section Abstract Doc Link 16847431 Disease Relevance 0.17 Pain Relevance 0.26
Young et al. reported an increase in interleukin-8 (IL-8) production after stimulating TLR3 and TLR4 in endometrial cell lines with appropriate ligands [12].
Positive_regulation (stimulating) of TLR4
6) Confidence 0.66 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 1.05 Pain Relevance 0.49
TLR3 recognizes RNA and viruses, whereas TLR4 mediates the response to bacterial endotoxins and is activated due to sterile inflammation [33,34].
Positive_regulation (activated) of TLR4 associated with inflammation
7) Confidence 0.66 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.51 Pain Relevance 0.09
Removal of these acylated SFAs from lipid A not only results in complete loss of endotoxic activity, but also makes the deacylated lipid A act as an antagonist to native lipid A, suggesting that the FAs that are acylated in lipid A play a crucial role in ligand recognition and receptor activation for TLR4.
Positive_regulation (activation) of TLR4 associated with antagonist
8) Confidence 0.65 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 0.26 Pain Relevance 0.18
Intake of high levels of fructose results in high triglyceride levels in plasma and their deposition in liver, as well as intestinal bacterial overgrowth and increased intestinal permeability, leading to elevated endotoxins and activation of TLR4 signaling [99,100].


Positive_regulation (activation) of TLR4 in liver
9) Confidence 0.65 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 1.14 Pain Relevance 0.42
Alcohol induces LBP and TLR4, and increases responsiveness to gut-derived endotoxin.
Positive_regulation (induces) of TLR4 in gut associated with alcohol
10) Confidence 0.65 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 1.04 Pain Relevance 0.47
Thus, TLR4 activation contributes to the obesity inflammatory process.
Positive_regulation (activation) of TLR4 associated with inflammation and obesity
11) Confidence 0.60 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2819999 Disease Relevance 1.09 Pain Relevance 0.18
Nevertheless, LPS requires one or several partner components to be present in the FBS in order to activate TLR4.
Positive_regulation (activate) of TLR4
12) Confidence 0.60 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2819999 Disease Relevance 0.16 Pain Relevance 0.03
In contrast, induction of macrophage maturation by M-CSF, has been shown to result in unchanged TLR2, increased TLR4 and very low TLR9 mRNA expression levels [40].
Positive_regulation (increased) of TLR4 in macrophage
13) Confidence 0.58 Published 2010 Journal Respir Res Section Body Doc Link PMC2817655 Disease Relevance 0.06 Pain Relevance 0.07
We and others [20], [22], [34], [43], [44] have shown that IEC of the mature, healthy small and large intestine express low levels of TLR4 and MD-2 and respond poorly to LPS, but TLR4 and MD-2 are abnormally upregulated in inflammatory bowel disease [34].
Positive_regulation (upregulated) of TLR4 in large intestine associated with inflammation
14) Confidence 0.57 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955554 Disease Relevance 0.99 Pain Relevance 0.21
Platelet-activating factor induces TLR4 promoter activation
Positive_regulation (activation) of TLR4 in Platelet
15) Confidence 0.57 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955554 Disease Relevance 0.10 Pain Relevance 0.10
Future experiments will elucidate the exact mechanisms of STAT3 involvement, and possibly other factors, in PAF mediated transcriptional activation of TLR4 and will investigate experimental models where PAF is neutralized.
Positive_regulation (activation) of TLR4
16) Confidence 0.57 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955554 Disease Relevance 0.47 Pain Relevance 0.16
Upon stimulation with PAF, a significant dose-dependent four-fold increase in TLR4 promoter activity (compared to unstimulated empty vector control) was observed (Figure 5).
Positive_regulation (increase) of TLR4
17) Confidence 0.57 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955554 Disease Relevance 0.08 Pain Relevance 0.08
We addressed the functionality of the induced TLR4 by exposing these cells to LPS.
Positive_regulation (induced) of TLR4
18) Confidence 0.57 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955554 Disease Relevance 0.14 Pain Relevance 0
We hypothesized that PAF, which is released due to hypoxia, infection, or local injury, induces an upregulation of TLR4 at the intestinal epithelium that predisposes to excessive bacterial activation of the intestinal inflammatory response, leading to intestinal necrosis and NEC.
Positive_regulation (upregulation) of TLR4 in intestinal epithelium associated with neonatal necrotizing enterocolitis, necrosis, inflammatory response, hypoxia, injury and infection
19) Confidence 0.57 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955554 Disease Relevance 1.30 Pain Relevance 0.18
Six hours post stimulation with cPAF, we observed a subsequent dose-dependent increase in TLR4 mRNA in Caco-2 cells using Real Time PCR analysis (Figure 2c).
Positive_regulation (increase) of TLR4 mRNA in Caco-2
20) Confidence 0.57 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955554 Disease Relevance 0.15 Pain Relevance 0

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