INT152730

Context Info Confidence 0.68 First Reported 2004 Last Reported 2011 Negated 1 Speculated 1 Reported most in Body Documents 48 Total Number 49 Disease Relevance 47.67 Pain Relevance 15.40

extracellular space (S100a8) extracellular region (S100a8) plasma membrane (S100a8) cytoskeleton (S100a8) cytoplasm (S100a8)

Anatomy Link Frequency bladder 5 kidney 5 keratinocytes 3 lungs 2 neutrophil 2 S100a8 (Mus musculus)

Pain Link Frequency Relevance Heat Inflammation 1293 100.00 cytokine 475 100.00 Inflammatory mediators 98 100.00 isoflurane 75 99.42 lidocaine 204 99.20 Paracetamol 12 99.18 Glutamate 12 98.12 Multiple sclerosis 93 98.00 dexamethasone 68 97.44 antagonist 17 96.88

Disease Link Frequency Relevance Heat INFLAMMATION 1555 100.00 Vasculitis 94 99.96 Injury 408 99.88 Urinary Tract Infection 588 99.84 Infection 602 99.76 Bacterial Respiratory Disease 29 99.72 Disease 257 99.44 Mycobacterial Infection 149 99.44 Apoptosis 293 99.38 Motor Neuron Diseases 86 98.04

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Key:

Protein

Mutation

Event

Anatomy

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Speculation

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Disease term

UTI resulted in a substantial increase of S100A8/A9 protein in bladder and kidney tissue of WT mice.

Positive_regulation (increase) of S100A8 in kidney associated with urinary tract infection

1) Confidence 0.68 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2954806 Disease Relevance 1.51 Pain Relevance 0.22

S100A8/A9 are found in granulocytes, monocytes and early differentiation stages of macrophages and can be induced in keratinocytes and epithelial cells under inflammatory conditions [9], [10].

Positive_regulation (induced) of S100A8 in keratinocytes associated with inflammation

2) Confidence 0.68 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2954806 Disease Relevance 1.05 Pain Relevance 0.21

As discussed previously, both the genes for MRP8 and its binding partner MRP14 are upregulated by wound-edge keratinocytes.

Positive_regulation (upregulated) of MRP8 in keratinocytes associated with injury

3) Confidence 0.66 Published 2005 Journal Genome Biol Section Body Doc Link PMC549066 Disease Relevance 1.36 Pain Relevance 0.28

Four hours after zymosan challenge, both S100A8 and S100A9 were significantly increased in the presence of lidocaine (Fig. 4A and Table 1).

Positive_regulation (increased) of S100A8 associated with lidocaine

4) Confidence 0.52 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2268966 Disease Relevance 0.38 Pain Relevance 0.70

The role of S100A8/A9 during a local infection of the urinary tract system caused by E. coli remains unknown.

Positive_regulation (role) of S100A8 associated with infection

5) Confidence 0.49 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2954806 Disease Relevance 1.24 Pain Relevance 0.17

The previous study [39] and our data oppose a role for S100A8/A9 in antibacterial defense mechanism.

Positive_regulation (role) of S100A8 associated with bacterial respiratory disease

6) Confidence 0.49 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2954806 Disease Relevance 0.67 Pain Relevance 0

The RT-QPCR analysis confirmed that neutrophil depletion in the mice significantly decreased, but did not completely abrogate the upregulation of the aforementioned genes (including S100A8, S100A9, IL-1?

Positive_regulation (upregulation) of S100A8 in neutrophil

7) Confidence 0.46 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2994359 Disease Relevance 0.50 Pain Relevance 0.12

Microarray profiling revealed that S100A4, S100A6, S100A8, S100A9, and S100A13 were upregulated in both CorNV models, with S100A8 and S100A9 manifesting the most significant changes compared to the normal animals.

Positive_regulation (upregulated) of S100A8

8) Confidence 0.46 Published 2010 Journal Molecular Vision Section Abstract Doc Link PMC2994359 Disease Relevance 0.65 Pain Relevance 0.21

As shown in figure 1A–B, S100A8/A9 level was higher in bladder and kidney homogenates from WT mice 24 and 48 hours after induction of UTI compared to sham mice.

Positive_regulation (induction) of S100A8 in kidney associated with urinary tract infection

9) Confidence 0.45 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2954806 Disease Relevance 0.29 Pain Relevance 0.06

As shown in figure 1A–B, S100A8/A9 level was higher in bladder and kidney homogenates from WT mice 24 and 48 hours after induction of UTI compared to sham mice.

Positive_regulation (higher) of S100A8 in kidney associated with urinary tract infection

10) Confidence 0.45 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2954806 Disease Relevance 0.28 Pain Relevance 0.06

The extent of upregulation of other detected S100A genes and pro-inflammatory or pro-angiogenic genes was also decreased by neutrophil depletion.

Positive_regulation (upregulation) of pro-inflammatory in neutrophil associated with inflammation

11) Confidence 0.40 Published 2010 Journal Molecular Vision Section Abstract Doc Link PMC2994359 Disease Relevance 0.49 Pain Relevance 0.23

We also found up-regulation of S100A8 and S100A9, which are expressed by activated keratinocytes in hyperproliferative epidermis of psoriatic patients and in epidermal skin cancers and which act as chemoattractants for inflammatory cells (Gebhardt et al., 2006).

Positive_regulation (up-regulation) of S100A8 in keratinocytes associated with psoriasis, inflammation and skin cancer

12) Confidence 0.38 Published 2010 Journal The Journal of Cell Biology Section Body Doc Link PMC2845079 Disease Relevance 0.72 Pain Relevance 0.43

Upregulation of S100A8 and S100A9 in premetastatic lung tissue provide a niche for migration of tumor cells [123].

Positive_regulation (Upregulation) of S100A8 in lung associated with cancer

13) Confidence 0.36 Published 2009 Journal J Transl Med Section Body Doc Link PMC2666642 Disease Relevance 0.60 Pain Relevance 0.07

Also, isoflurane selectively reduced zymosan-stimulated pro-inflammatory cytokine levels (Fig. 7B and Tables 6 and 7), which contrasts the events in mice treated with zymosan and anesthetic dose of lidocaine (0.08%), that significantly reduced anti-inflammatory IL-13 (Fig. 5B).

Positive_regulation (stimulated) of pro-inflammatory associated with inflammation, isoflurane, lidocaine and cytokine

14) Confidence 0.33 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2268966 Disease Relevance 0.98 Pain Relevance 1.12

Our data show that both S100A8 and S100A9 are induced in the D12-M.tuberculosis-infected lungs (Table 7).

Positive_regulation (induced) of S100A8 in lungs associated with mycobacterial infection

15) Confidence 0.27 Published 2011 Journal PLoS ONE Section Body Doc Link PMC3020951 Disease Relevance 1.59 Pain Relevance 0.13

S100A8/A9 are found in granulocytes, monocytes and early differentiation stages of macrophages and can be induced in keratinocytes and epithelial cells under inflammatory conditions [9], [10].

Positive_regulation (induced) of S100A8 in epithelial cells associated with inflammation

16) Confidence 0.23 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2954806 Disease Relevance 1.05 Pain Relevance 0.21

UTI resulted in a substantial increase of S100A8/A9 protein in bladder and kidney tissue of WT mice.

Positive_regulation (increase) of S100A8 in bladder associated with urinary tract infection

17) Confidence 0.23 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2954806 Disease Relevance 1.51 Pain Relevance 0.22

High levels of S100A8/A9 were observed in bladder and kidney tissue during UTI.

Positive_regulation (levels) of S100A8 in kidney associated with urinary tract infection

18) Confidence 0.20 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2954806 Disease Relevance 2.09 Pain Relevance 0.13

These data are in line with our results demonstrating that during UTI, levels of S100A8/A9 increased in both bladder and kidney homogenates.

Positive_regulation (increased) of S100A8 in bladder associated with urinary tract infection

19) Confidence 0.20 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2954806 Disease Relevance 0.99 Pain Relevance 0.11

As shown in figure 1A–B, S100A8/A9 level was higher in bladder and kidney homogenates from WT mice 24 and 48 hours after induction of UTI compared to sham mice.

Positive_regulation (higher) of S100A8 in bladder associated with urinary tract infection

20) Confidence 0.15 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2954806 Disease Relevance 0.28 Pain Relevance 0.06

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