INT117223

Context Info Confidence 0.78 First Reported 2003 Last Reported 2011 Negated 4 Speculated 12 Reported most in Abstract Documents 348 Total Number 362 Disease Relevance 206.18 Pain Relevance 54.42

signal transduction (TLR4) plasma membrane (TLR4) intracellular (TLR4) cytoplasm (TLR4)

Anatomy Link Frequency monocytes 34 macrophages 19 epithelial cells 13 alveolar macrophages 13 T cells 13 TLR4 (Homo sapiens) TLR4 - T399I (1) TLR4 - D299G (1)

Pain Link Frequency Relevance Heat agonist 2046 100.00 COX2 7 100.00 spinal inflammation 481 99.96 cytokine 4493 99.92 depression 15 99.92 tolerance 296 99.86 Arthritis 1465 99.84 Bile 188 99.84 endometriosis 758 99.78 addiction 51 99.68

Disease Link Frequency Relevance Heat Cancer 620 100.00 Necrosis 454 100.00 Cirrhosis 2074 99.98 Obesity 607 99.98 Low Back Pain 481 99.96 Carcinoma 305 99.96 Biliary Liver Cirrhosis 136 99.96 Pancreatitis 30 99.96 Atherosclerosis 178 99.92 Coronary Artery Disease 93 99.92

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In mild AP, TLR4 expression increased on the first day of admission and then continued to decline for several days.

Gene_expression (expression) of TLR4 associated with pancreatitis

1) Confidence 0.78 Published 2007 Journal Dig. Dis. Sci. Section Abstract Doc Link 17415654 Disease Relevance 0.69 Pain Relevance 0.08

On the seventh day, TLR4 expression was almost normal compared with that of the normal control.

Gene_expression (expression) of TLR4

2) Confidence 0.78 Published 2007 Journal Dig. Dis. Sci. Section Abstract Doc Link 17415654 Disease Relevance 0.66 Pain Relevance 0.08

Alterations of Toll-like receptor 4 expression on peripheral blood monocytes during the early stage of human acute pancreatitis.

Gene_expression (expression) of Toll-like receptor 4 in monocytes associated with pancreatitis

3) Confidence 0.78 Published 2007 Journal Dig. Dis. Sci. Section Title Doc Link 17415654 Disease Relevance 0.68 Pain Relevance 0.09

PBMCs were isolated, and TLR4 and CD14 expression on PBMCs was detected by flow cytometer.

Gene_expression (expression) of TLR4

4) Confidence 0.78 Published 2007 Journal Dig. Dis. Sci. Section Abstract Doc Link 17415654 Disease Relevance 0.71 Pain Relevance 0.09

We sought to study Toll-like receptor 4 (TLR4) expression on peripheral blood mononuclear cells (PBMCs) during the early stage of human acute pancreatitis (AP).

Gene_expression (expression) of Toll-like receptor 4 in mononuclear cells associated with pancreatitis

5) Confidence 0.78 Published 2007 Journal Dig. Dis. Sci. Section Abstract Doc Link 17415654 Disease Relevance 0.62 Pain Relevance 0.08

We sought to study Toll-like receptor 4 (TLR4) expression on peripheral blood mononuclear cells (PBMCs) during the early stage of human acute pancreatitis (AP).

Gene_expression (expression) of TLR4 in mononuclear cells associated with pancreatitis

6) Confidence 0.78 Published 2007 Journal Dig. Dis. Sci. Section Abstract Doc Link 17415654 Disease Relevance 0.62 Pain Relevance 0.08

We investigated whether the TLR4 expression levels on human peripheral blood monocytes were associated with serum hsCRP levels or the occurrence of coronary artery diseases (CAD).

Gene_expression (expression) of TLR4 in blood associated with coronary artery disease

7) Confidence 0.77 Published 2006 Journal Life Sci. Section Abstract Doc Link 17045300 Disease Relevance 1.06 Pain Relevance 0.12

The combined measurement of serum hsCRP and the TLR4 expression on peripheral blood monocytes, especially among low-hsCRP subjects, may become a new coronary risk marker.

Gene_expression (expression) of TLR4 in monocytes

8) Confidence 0.77 Published 2006 Journal Life Sci. Section Abstract Doc Link 17045300 Disease Relevance 1.41 Pain Relevance 0.25

Among the low-hsCRP subjects, the TLR4 expression levels were higher in CAD patients than in non-CAD subjects (P < 0.05, after being adjusted for other risk factors).

Gene_expression (expression) of TLR4 associated with coronary artery disease

9) Confidence 0.77 Published 2006 Journal Life Sci. Section Abstract Doc Link 17045300 Disease Relevance 1.51 Pain Relevance 0.25

In conclusion, the TLR4 expression levels on peripheral blood monocytes in CAD patients were higher than those in non-CAD subjects and correlated with disease activity, even in low-hsCRP subjects.

Gene_expression (expression) of TLR4 in monocytes associated with coronary artery disease and disease

10) Confidence 0.77 Published 2006 Journal Life Sci. Section Abstract Doc Link 17045300 Disease Relevance 1.54 Pain Relevance 0.28

Toll-like receptor 4 expressions on peripheral blood monocytes were enhanced in coronary artery disease even in patients with low C-reactive protein.

Gene_expression (expressions) of Toll-like receptor 4 in coronary artery associated with coronary artery disease

11) Confidence 0.77 Published 2006 Journal Life Sci. Section Title Doc Link 17045300 Disease Relevance 1.14 Pain Relevance 0.18

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).

Gene_expression (expression) of TLR4 associated with stable angina pectoris, acute coronary syndrome, angina and coronary artery disease

12) Confidence 0.77 Published 2006 Journal Life Sci. Section Abstract Doc Link 17045300 Disease Relevance 1.57 Pain Relevance 0.29

Almost all therapeutic vaccine adjuvant approaches use ligands for one of the Toll-like receptors (TLR) expressed on DC.

Gene_expression (expressed) of Toll

13) Confidence 0.75 Published 2007 Journal J Immune Based Ther Vaccines Section Body Doc Link PMC1852106 Disease Relevance 0.17 Pain Relevance 0.13

Macrophages and dendritic cells (DCs) express numerous Toll-like receptors (TLRs) [10] and respond to microbial pathogens by producing type I interferons (IFN) and cytokines.

Gene_expression (express) of Toll in dendritic cells associated with cytokine

14) Confidence 0.75 Published 2008 Journal International Journal of Molecular Sciences Section Body Doc Link PMC2635754 Disease Relevance 0.68 Pain Relevance 0.05

Recently, there is research effort to elucidate the unknown mechanism that drives the regulation of TLR4 expression [61] and research findings [62] support the potential role of pro-inflammatory cytokines to up-regulate the TLR expression.

Gene_expression (expression) of TLR4 associated with inflammation and cytokine

15) Confidence 0.75 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2651450 Disease Relevance 0.25 Pain Relevance 0.21

Thus, the predominant expression of TLR4, observed in uterine tissues, might reflect the occurrence of sterile inflammation during the menstrual cycle.

Gene_expression (expression) of TLR4 in uterine associated with inflammation

16) Confidence 0.74 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.44 Pain Relevance 0.10

We propose that the sterile inflammation process, which occurs in the pelvic cavity upon endometriosis, is able to enhance the epithelial TLR4 expression and thus activate the known downstream signalling cascade.

Gene_expression (expression) of TLR4 in cavity associated with endometriosis and inflammation

17) Confidence 0.74 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 1.20 Pain Relevance 0.31

Co-immunostainings on menstrual effluents confirmed that CD14 positive dendritic cells and monocytes (figure 2K) as well as CD163 positive resident macrophages (figure 2L) expressed TLR4 protein.

Gene_expression (expressed) of TLR4 protein in macrophages

18) Confidence 0.74 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.31 Pain Relevance 0.08

In addition, we report the expression of TLR4 protein on immune cells such as monocytes and macrophages, in menstrual phase samples (figure 2J).

Gene_expression (expression) of TLR4 protein in macrophages

19) Confidence 0.74 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.21 Pain Relevance 0.07

TLR3 and TLR4 expression is deregulated in peritoneal endometriosis

Gene_expression (expression) of TLR4 associated with endometriosis

20) Confidence 0.74 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.10 Pain Relevance 0.05

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