INT143159

Context Info Confidence 0.62 First Reported 2005 Last Reported 2010 Negated 6 Speculated 3 Reported most in Body Documents 28 Total Number 31 Disease Relevance 15.08 Pain Relevance 3.54

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

Anatomy Link Frequency monocytes 6 alveolar macrophages 6 macrophages 4 TLR4 (Homo sapiens)

Pain Link Frequency Relevance Heat cytokine 395 100.00 addiction 4 100.00 spinal inflammation 3 100.00 Inflammation 382 99.84 endometriosis 21 99.40 Inflammatory response 123 98.16 rheumatoid arthritis 186 96.08 abdominal pain 2 93.04 Inflammatory mediators 26 87.20 chemokine 40 86.28

Disease Link Frequency Relevance Heat Low Back Pain 3 100.00 INFLAMMATION 523 99.84 Nicotine Addiction 264 99.64 Endometriosis (extended) 38 99.40 Pulmonary Disease 162 98.76 Mycobacterial Infection 216 98.48 Cv General 3 Under Development 1 98.40 Cancer 23 97.92 Osteoarthritis 102 97.56 Pancreatitis 10 97.48

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

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

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

1) Confidence 0.62 Published 2007 Journal Dig. Dis. Sci. Section Title Doc Link 17415654 Disease Relevance 0.68 Pain Relevance 0.09

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.

Spec (findings) Regulation (regulation) of Gene_expression (expression) of TLR4 associated with inflammation and cytokine

2) Confidence 0.60 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2651450 Disease Relevance 0.25 Pain Relevance 0.21

TLR3 and TLR4 expression is deregulated in peritoneal endometriosis

Regulation (deregulated) of Gene_expression (expression) of TLR4 associated with endometriosis

3) Confidence 0.59 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2543020 Disease Relevance 0.10 Pain Relevance 0.05

While TLR2 regulation may be due to Pam3Cys ligation and/or cytokine production from macrophages or other cellular subsets within the bronchoalveolar cells (5-8% are lymphocytes), regulation of TLR4 expression may result from a direct effect of LPS on the cell membrane as it was noted already within 10 minutes of LPS stimulation.

Regulation (regulation) of Gene_expression (expression) of TLR4 in macrophages associated with cytokine

4) Confidence 0.51 Published 2010 Journal Respir Res Section Body Doc Link PMC2817655 Disease Relevance 0.08 Pain Relevance 0.12

These observations imply that luminal exposure of PAF can lead to changes in TLR4 expression and signaling.

Regulation (changes) of Gene_expression (expression) of TLR4

5) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955554 Disease Relevance 0.42 Pain Relevance 0

B is both a downstream effector of TLR signaling and it is an upstream regulator of TLR4 expression, making this transcription factor a central molecule in inflammatory regulation.

Regulation (regulator) of Gene_expression (expression) of TLR4 associated with inflammation

6) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955554 Disease Relevance 0.21 Pain Relevance 0.08

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

Regulation (detected) of Gene_expression (expression) of TLR4

7) Confidence 0.45 Published 2007 Journal Dig. Dis. Sci. Section Abstract Doc Link 17415654 Disease Relevance 0.72 Pain Relevance 0.09

There was no abnormality in mRNA expression of TLR2 and TLR4 in PMNs (Figure 2c,d).

Neg (no) Regulation (abnormality) of Gene_expression (expression) of TLR4

8) Confidence 0.44 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2374472 Disease Relevance 0.62 Pain Relevance 0.04

Human cholangiocytes express members of the let-7 miRNA family, at least one of which, let-7i, directly regulates TLR4 expression via a MyD88-NF-?

Regulation (regulates) of Gene_expression (expression) of TLR4

9) Confidence 0.42 Published 2010 Journal Fibrogenesis Tissue Repair Section Body Doc Link PMC2984459 Disease Relevance 0.13 Pain Relevance 0.19

Regulation of TLR4 expression by IFN?

Regulation (Regulation) of Gene_expression (expression) of TLR4

10) Confidence 0.40 Published 2007 Journal Molecular Vision Section Body Doc Link PMC2768757 Disease Relevance 0.45 Pain Relevance 0.19

TLR2, TLR4 and TLR9 mRNA expression in monocyte-derived and alveolar macrophages

Regulation (alveolar macrophages) of Gene_expression (expression) of TLR4 in alveolar macrophages

11) Confidence 0.38 Published 2010 Journal Respir Res Section Body Doc Link PMC2817655 Disease Relevance 0 Pain Relevance 0

The present work therefore aimed at characterizing the expression of TLR2, TLR4 and TLR9 on human alveolar macrophages.

Regulation (characterizing) of Gene_expression (expression) of TLR4 in alveolar macrophages

12) Confidence 0.38 Published 2010 Journal Respir Res Section Body Doc Link PMC2817655 Disease Relevance 0.36 Pain Relevance 0

No further changes of TLR2 and TLR4 surface expression had been observed within a 24-hour observation period in our pilot study (data not shown).

Neg (No) Regulation (changes) of Gene_expression (expression) of TLR4

13) Confidence 0.38 Published 2010 Journal Respir Res Section Body Doc Link PMC2817655 Disease Relevance 0.23 Pain Relevance 0

Taken together these results indicate a differential, cell-type-specific ligand-mediated regulation of the expression of TLR2 and TLR4.

Regulation (regulation) of Gene_expression (expression) of TLR4

14) Confidence 0.38 Published 2010 Journal Respir Res Section Body Doc Link PMC2817655 Disease Relevance 0.05 Pain Relevance 0.15

Quantitative real-time PCR (qRT-PCR, TaqMan) was performed to determine the relative TLR2, TLR4 and TLR9 mRNA expression levels using the comparative threshold cycle (??

Spec (determine) Regulation (using) of Spec (determine) Gene_expression (expression) of TLR4

15) Confidence 0.38 Published 2010 Journal Respir Res Section Body Doc Link PMC2817655 Disease Relevance 0 Pain Relevance 0

TLR2, TLR4 and TLR9 mRNA expression in monocyte-derived and alveolar macrophages

Regulation (monocyte) of Gene_expression (expression) of TLR4 in alveolar macrophages

16) Confidence 0.38 Published 2010 Journal Respir Res Section Body Doc Link PMC2817655 Disease Relevance 0 Pain Relevance 0

B binding sites [29], it is not surprising that we observed a dependence of PAF-induced TLR4 gene expression on NF-?

Regulation (dependence) of Gene_expression (expression) of TLR4 gene associated with addiction

17) Confidence 0.37 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955554 Disease Relevance 0.37 Pain Relevance 0.13

There was no difference in the expression of CD14 and TLR4 between the groups (CD14: 5 ± 1.56 and 4,7 ± 1,6 vs. 4.09 ± 0.69 and 4.3 ± 1.53 rMFI; TLR4: 5.19 ± 1.58 and 5,3 ± 2,1 vs. 4.28 ± 0.7 and 4.62 ± 1.38 rMFI, respectively).

Neg (no) Regulation (difference) of Gene_expression (expression) of TLR4

18) Confidence 0.35 Published 2005 Journal Respir Res Section Body Doc Link PMC1187924 Disease Relevance 1.17 Pain Relevance 0

In contrast, no difference in TLR4 expression between smokers, non-smokers, COPD patients was observed in our study which may be due to the generally weaker expression of this molecule on monocytes and AM.

Neg (no) Regulation (difference) of Gene_expression (expression) of TLR4 in monocytes associated with pulmonary disease and nicotine addiction

19) Confidence 0.35 Published 2005 Journal Respir Res Section Body Doc Link PMC1187924 Disease Relevance 0.96 Pain Relevance 0.05

Effect of cytokines and LPS on TLR2 and TLR4 gene expression in PBMCs

Regulation (Effect) of Gene_expression (expression) of TLR4 associated with cytokine

20) Confidence 0.32 Published 2008 Journal Mediators of Inflammation Section Body Doc Link PMC2435281 Disease Relevance 0.87 Pain Relevance 0.34

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