INT82448

Context Info Confidence 0.77 First Reported 1999 Last Reported 2011 Negated 5 Speculated 1 Reported most in Body Documents 246 Total Number 248 Disease Relevance 236.72 Pain Relevance 84.02

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

Anatomy Link Frequency macrophages 21 neutrophil 13 microglia 11 bladder 10 keratinocytes 7 S100a8 (Mus musculus)

Pain Link Frequency Relevance Heat Inflammation 7006 100.00 cytokine 3260 100.00 chemokine 734 100.00 Inflammatory mediators 362 100.00 Inflammatory stimuli 60 100.00 Inflammatory marker 25 100.00 member 8 14 100.00 Central nervous system 413 99.98 IPN 48 99.92 Inflammatory response 678 99.90

Disease Link Frequency Relevance Heat INFLAMMATION 7931 100.00 Mycobacterial Infection 604 100.00 Multiple Sclerosis 443 100.00 Obesity 983 99.98 Pleurisy 22 99.98 Chemotherapy-induced Neutropenia 15 99.98 Urinary Tract Infection 1092 99.96 Inflammatory Pain 51 99.92 Pressure And Volume Under Development 194 99.90 Pneumonia 118 99.90

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Anatomy

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Depletion of neutrophils abrogated S-CorNV and S100A8 and S100A9 production

Gene_expression (production) of S100A8 in neutrophils

1) Confidence 0.77 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2994359 Disease Relevance 0.46 Pain Relevance 0.08

We further showed that depletion of neutrophils decreased S100A8 and S100A9 expression in S-CorNV corneas compared to control S-CorNV corneas (Figure 3).

Gene_expression (expression) of S100A8 in corneas associated with chemotherapy-induced neutropenia

2) Confidence 0.77 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2994359 Disease Relevance 0.49 Pain Relevance 0.11

Recently, S100A6, S100A8, and S100A9 were found to be extensively expressed in pterygium tissue removed from patients [41,42].

Gene_expression (expressed) of S100A8 associated with conjunctiva disease

3) Confidence 0.77 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2994359 Disease Relevance 0.84 Pain Relevance 0.16

The expression of S100A8/A9 has been investigated in several infection models.

Gene_expression (expression) of S100A8 associated with infection

4) Confidence 0.76 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2954806 Disease Relevance 1.38 Pain Relevance 0.17

We show that despite high S100A8/A9 expression in bladder and kidney tissue upon UTI, in this model S100A8/A9 does not contribute to an effective host response against E.

Gene_expression (expression) of S100A8 in kidney associated with urinary tract infection

5) Confidence 0.76 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2954806 Disease Relevance 1.08 Pain Relevance 0.12

We anticipate that the S100A8/A9 expression we found originated from infiltrating granulocytes at infected areas.

Gene_expression (expression) of S100A8 in granulocytes

6) Confidence 0.76 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2954806 Disease Relevance 0.91 Pain Relevance 0.10

Of these S100 proteins, S100A8/A9 are of special interest because S100A8/A9 complexes induce an inflammatory response and S100A8/A9 expression correlates with disease severity in several inflammatory disorders [9], [15].

Gene_expression (expression) of S100A8 associated with inflammatory response, inflammation and disease

7) Confidence 0.76 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2954806 Disease Relevance 1.44 Pain Relevance 0.17

In addition, U. parvum-induced complicated UTI in rats, leads to higher expression of S100A8/A9 complex in bladder tissue compared to bladders from animals with asymptomatic UTI [17].

Gene_expression (expression) of S100A8 in bladders associated with urinary tract infection

8) Confidence 0.76 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2954806 Disease Relevance 1.17 Pain Relevance 0.15

CP-10, a chemotactic peptide, is expressed in lesions of experimental autoimmune encephalomyelitis, neuritis, uveitis and in C6 gliomas.

Gene_expression (expressed) of CP-10 associated with multiple sclerosis, uveitis, neuritis and glioma

9) Confidence 0.75 Published 1999 Journal J. Neuroimmunol. Section Title Doc Link 10378879 Disease Relevance 1.02 Pain Relevance 0.28

Using double labeling experiments, other cells participating in the inflammatory reaction were found to express CP-10, like few lymphoblastic W3/13+ cells in the vicinity of the inflammatory infiltrate.

Gene_expression (express) of CP-10 associated with inflammation

10) Confidence 0.75 Published 1999 Journal J. Neuroimmunol. Section Abstract Doc Link 10378879 Disease Relevance 1.16 Pain Relevance 0.29

It is concluded that this mouse model with infection by the CagA-positive, vac-toxin-producing H. pylori strain 119/95 is suitable for use in the study of lymphoma development and also development of squamous cell papilloma with proliferative features.

Gene_expression (producing) of CagA associated with lymphatic system cancer, sprains and strains, papilloma and infection

11) Confidence 0.75 Published 2000 Journal APMIS Section Abstract Doc Link 11167546 Disease Relevance 1.73 Pain Relevance 0.06

In situ hybridization clearly shows MRP14 to be expressed, in addition to expression in keratinocytes, in the region of the wound populated by inflammatory cells in the wild-type only (Figure 7Ak,l), and indeed, previous experiments suggest that both neutrophils and macrophages express MRP8 and MRP14 [22].

Gene_expression (express) of MRP8 in keratinocytes associated with inflammation and injury

12) Confidence 0.73 Published 2005 Journal Genome Biol Section Body Doc Link PMC549066 Disease Relevance 1.18 Pain Relevance 0.26

Interestingly, another member of the late effector cluster, the intracellular Ca2+-binding protein MRP8 (S100A8) is expressed in a similar temporal and spatial pattern to K6 (Figure 4o and 4p).

Gene_expression (expressed) of S100A8

13) Confidence 0.73 Published 2005 Journal Genome Biol Section Body Doc Link PMC549066 Disease Relevance 0.51 Pain Relevance 0

The temporal and spatial coexpression of K6 with MRP8 may highlight a relationship between them and as such reveals another advantage of cluster analysis - the ability to identify potential interactions between genes and genetic pathways within the same cluster.

Gene_expression (coexpression) of MRP8

14) Confidence 0.73 Published 2005 Journal Genome Biol Section Body Doc Link PMC549066 Disease Relevance 0.46 Pain Relevance 0.03

Interestingly, another member of the late effector cluster, the intracellular Ca2+-binding protein MRP8 (S100A8) is expressed in a similar temporal and spatial pattern to K6 (Figure 4o and 4p).

Gene_expression (expressed) of MRP8

15) Confidence 0.73 Published 2005 Journal Genome Biol Section Body Doc Link PMC549066 Disease Relevance 0.51 Pain Relevance 0

Immunohistochemistry analysis of the S-CorNV corneas showed that S100A8 and S100A9 were deposited in the neovascularized corneas (Figure 2).

Gene_expression (deposited) of S100A8 in corneas

16) Confidence 0.67 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2994359 Disease Relevance 0.28 Pain Relevance 0.07

To conclude, we found that S100A8 and S100A9 were involved in the inflammatory CorNV model.

Gene_expression (involved) of S100A8 associated with inflammation

17) Confidence 0.67 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2994359 Disease Relevance 0.59 Pain Relevance 0.17

Considering the above observation that S100A8 and S100A9 proteins are located in both neutrophils and macrophages (Figure 2), we suggest that S100A8 (and S100A9) produced by neutrophils attracted more neutrophils in turn, thus forming a positive feedback in certain stages of inflammatory CorNV.

Gene_expression (produced) of S100A8 in neutrophils associated with inflammation

18) Confidence 0.67 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2994359 Disease Relevance 0.41 Pain Relevance 0.18

Thus comparative studies of mice that are deficient in S100A8 or S100A9 (e.g., gene knockout mice of such genes) will help to determine how these two genes take their effects in the development of CorNV under various conditions.

Gene_expression (deficient) of S100A8 associated with targeted disruption

19) Confidence 0.67 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2994359 Disease Relevance 0.38 Pain Relevance 0.11

Subconjunctival injection of anti-S100A8 mAb

Gene_expression (mAb) of S100A8

20) Confidence 0.67 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2994359 Disease Relevance 0 Pain Relevance 0

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