INT137178

Context Info Confidence 0.72 First Reported 2005 Last Reported 2010 Negated 1 Speculated 1 Reported most in Body Documents 46 Total Number 47 Disease Relevance 24.97 Pain Relevance 4.33

endosome (TLR3) signal transduction (TLR3) endoplasmic reticulum (TLR3) intracellular (TLR3) cytoplasm (TLR3)

Anatomy Link Frequency endometrium 8 epithelial cells 6 poly 2 T-cell 2 middle ear 1 TLR3 (Homo sapiens)

Pain Link Frequency Relevance Heat endometriosis 462 99.96 Inflammation 552 99.54 cytokine 482 99.36 agonist 39 98.36 chemokine 121 97.20 Inflammatory response 30 90.28 Arthritis 22 88.04 tolerance 5 77.92 pain pelvic 22 67.92 Dismenorea 22 66.88

Disease Link Frequency Relevance Heat Skin Cancer 33 100.00 Endometriosis (extended) 837 99.96 Carcinoma 176 99.96 Infection 431 99.74 Disease 328 99.66 Uterine Diseases 110 99.56 INFLAMMATION 572 99.54 Cold Sores 1107 99.50 Increased Venous Pressure Under Development 4 98.82 Hyperplasia 66 98.44

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Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

TLR3 and TLR4 mRNA expression varied significantly between control, hyperplasia and endometrial adenocarcinoma samples (Kruskal-Wallis test, P < 0.01).

Gene_expression (expression) of TLR3 associated with endometriosis (extended) and hyperplasia

1) Confidence 0.72 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.79 Pain Relevance 0.07

Indeed, the TLR3 receptor was found to be locally expressed in a subset of epithelial cells within one gland.

Gene_expression (expressed) of TLR3 receptor in epithelial cells

2) Confidence 0.72 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.20 Pain Relevance 0.07

TLR3 and TLR4 proteins were expressed mainly in the luminal and glandular epithelium (figure 2).

Gene_expression (expressed) of TLR3 in epithelium

3) Confidence 0.72 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.14 Pain Relevance 0.07

TLR3 and TLR4 expression is deregulated in peritoneal endometriosis

Gene_expression (expression) of TLR3 associated with endometriosis

4) Confidence 0.72 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.10 Pain Relevance 0.05

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].

Gene_expression (expression) of TLR3 in epithelial cells associated with cytokine

5) Confidence 0.72 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.67 Pain Relevance 0.34

In the current study, we report that toll-like receptor 3 and 4 expression is modulated in pathogenic alterations of the endometrium.

Gene_expression (expression) of toll-like receptor 3 in endometrium

6) Confidence 0.72 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.69 Pain Relevance 0.06

TLR3 and TLR4 are expressed in postmenopausal endometrium and regulated endometrial adenocarcinoma

Gene_expression (expressed) of TLR3 in endometrium associated with endometriosis (extended)

7) Confidence 0.72 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.64 Pain Relevance 0.09

Figure 4 exemplary presents the expression of TLR3 and TLR4 protein in eutopic compared to ectopic endometrium from the same patient.

Gene_expression (expression) of TLR3 in endometrium

8) Confidence 0.72 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.43 Pain Relevance 0.11

For the first time, we present endometrial effluents expressing high levels of TLR3 and TLR4 proteins.

Gene_expression (expressing) of TLR3

9) Confidence 0.72 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.27 Pain Relevance 0.06

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).

Gene_expression (levels) of TLR3 associated with endometriosis

10) Confidence 0.63 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.32 Pain Relevance 0.08

In undifferentiated G3 carcinoma, TLR3 and TLR4 mRNA levels were significantly lower than in postmenopausal controls (P < 0.01) and in hyperplasic endometrial tissues (P < 0.05, figure 5C–D).

Gene_expression (levels) of TLR3 associated with carcinoma

11) Confidence 0.63 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.92 Pain Relevance 0.04

In undifferentiated G3 carcinoma, staining for TLR3 (figure 6E) and TLR4 (figure 6J) was not detectable, strengthening our findings of low TLR3 and TLR4 mRNA abundance in G3 carcinoma (figure 5B).

Gene_expression (staining) of TLR3 associated with carcinoma

12) Confidence 0.63 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 1.01 Pain Relevance 0

For the first time, we present endometrial effluents expressing high levels of TLR3 and TLR4 proteins.

Gene_expression (expressing) of TLR3

13) Confidence 0.63 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.27 Pain Relevance 0.06

The increased expression of TLR2, TLR3 and TLR4 as a consequence of allergen exposure is in line with a previous report demonstrating an increase of TLR2 protein in chronic middle ear inflammation [26].

Gene_expression (expression) of TLR3 in middle ear associated with otitis media and inflammation

14) Confidence 0.60 Published 2005 Journal Respir Res Section Body Doc Link PMC1243240 Disease Relevance 0.45 Pain Relevance 0.10

In patients with peritoneal endometriosis, TLR3 and TLR4 mRNA expression decreased significantly in proliferative diseased endometrium compared to controls.

Gene_expression (expression) of TLR3 in endometrium associated with endometriosis

15) Confidence 0.56 Published 2008 Journal Reprod Biol Endocrinol Section Abstract Doc Link PMC2543020 Disease Relevance 0.78 Pain Relevance 0.09

In most tissues including gut, gonads and placenta, TLR3 is greater expressed than TLR4 mRNA [32].

Gene_expression (expressed) of TLR3 in placenta

16) Confidence 0.56 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.50 Pain Relevance 0.08

TLR3 and TLR4 expression was investigated during the menstrual cycle and in postmenopausal endometrium considering peritoneal endometriosis, hyperplasia, and endometrial adenocarcinoma specimens (grade 1 to 3).

Gene_expression (expression) of TLR3 in endometrium associated with endometriosis, endometriosis (extended) and hyperplasia

17) Confidence 0.56 Published 2008 Journal Reprod Biol Endocrinol Section Abstract Doc Link PMC2543020 Disease Relevance 0.44 Pain Relevance 0.07

TLR3 and TLR4 expression in healthy and diseased human endometrium Background

Gene_expression (expression) of TLR3 in endometrium

18) Confidence 0.56 Published 2008 Journal Reprod Biol Endocrinol Section Title Doc Link PMC2543020 Disease Relevance 0.45 Pain Relevance 0.07

Healthy and differentiated endometrium seems to require an adequate TLR3 and TLR4 expression.

Gene_expression (expression) of TLR3 in endometrium

19) Confidence 0.56 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.77 Pain Relevance 0.05

However, peptidoglycan (PGN), double-stranded (ds) RNA or lipopolysaccharide (LPS) (TLR2, TLR3 or TLR4 ligands, respectively) synergized with interferon-gamma (IFN-gamma) at inducing CXCL9 and CXCL10.

Gene_expression (synergized) of TLR3

20) Confidence 0.56 Published 2006 Journal Lab. Invest. Section Abstract Doc Link 16847431 Disease Relevance 0.30 Pain Relevance 0.27

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