INT248177

Context Info Confidence 0.79 First Reported 2008 Last Reported 2009 Negated 0 Speculated 0 Reported most in Body Documents 17 Total Number 17 Disease Relevance 4.87 Pain Relevance 2.82

endosome (Cxcr4) cytoplasmic membrane-bounded vesicle (Cxcr4) plasma membrane (Cxcr4) signal transducer activity (Cxcr4)

Anatomy Link Frequency bladder 5 plasma 1 IB4 1 apical ends 1 Cxcr4 (Rattus norvegicus)

Pain Link Frequency Relevance Heat anesthesia 15 99.60 chemokine 346 97.88 Inflammation 511 92.84 cytokine 100 85.88 dorsal root ganglion 103 84.40 Stimulus evoked pain 30 77.40 Lasting pain 19 65.36 cva 15 63.88 Peripheral nerve injury 3 58.92 Pain 20 51.84

Disease Link Frequency Relevance Heat Cystitis 255 97.80 INFLAMMATION 531 92.84 Injury 124 88.12 Ganglion Cysts 103 84.40 Hypersensitivity 34 77.40 Pain 65 76.72 Body Weight 76 73.04 Hyperplasia 30 70.84 Hemorrhage 15 63.88 Pressure And Volume Under Development 16 61.48

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

After CYP-treatment, MIF and CXCR4 are readily localized throughout the urothelium (Fig 4D–I), even on superficial cells previously devoid of MIF or CXCR4 (arrows in Fig 4F,I).

Localization (localized) of CXCR4

1) Confidence 0.79 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2588654 Disease Relevance 0 Pain Relevance 0

In saline-treated rats, both MIF and CXCR4 could be localized in the basal and intermediate layers of the urothelium (but not in superficial cells) (Fig 4A–C).

Localization (localized) of CXCR4

2) Confidence 0.79 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2588654 Disease Relevance 0 Pain Relevance 0

Bladder CXCR4 and CXCR4-MIF co-localization were examined with immunhistochemistry.

Localization (localization) of CXCR4 in Bladder

3) Confidence 0.79 Published 2008 Journal PLoS ONE Section Abstract Doc Link PMC2588654 Disease Relevance 0.43 Pain Relevance 0.22

CXCR4 and MIF are co-localized in cells in the urothelium and CYP induced co-localization of CXCR4 and MIF to superficial cells of the urothelium.

Localization (localization) of CXCR4

4) Confidence 0.79 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2588654 Disease Relevance 0.57 Pain Relevance 0.45

Using dual immunohistochemistry we show that MIF and CXCR4 are colocalized within the same cells in the urothelium and co-immunoprecipitation studies demonstrate MIF-CXCR4 associations in the bladder.

Localization (colocalized) of CXCR4 in bladder

5) Confidence 0.79 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2588654 Disease Relevance 0.73 Pain Relevance 0.12

Bladder CXCR4 and CXCR4-MIF co-localization were examined with immunhistochemistry.

Localization (localization) of CXCR4 in Bladder

6) Confidence 0.79 Published 2008 Journal PLoS ONE Section Abstract Doc Link PMC2588654 Disease Relevance 0.43 Pain Relevance 0.23

CXCR4 immunostaining in urothelium: co-localization with MIF and effect of treatment with cyclophosphamide

Localization (localization) of CXCR4

7) Confidence 0.73 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2588654 Disease Relevance 0.26 Pain Relevance 0.06

In this study we confirm these in vitro finding since we demonstrate 1) co-localization of CXCR4 and MIF in the urothelium, both in saline treated rats and after CYP treatment; 2) CXCR4-MIF associations are present in saline-treated bladder and increase after CYP treatment.

Localization (localization) of CXCR4 in bladder

8) Confidence 0.73 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2588654 Disease Relevance 0.38 Pain Relevance 0.31

CXCR4 and MIF are co-localized in cells in the urothelium and CYP induced co-localization of CXCR4 and MIF to superficial cells of the urothelium.

Localization (localized) of CXCR4

9) Confidence 0.73 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2588654 Disease Relevance 0.64 Pain Relevance 0.51

We examined the co-localization of CXCR4 and MIF in the urothelium using dual-immunofluorescence.

Localization (localization) of CXCR4

10) Confidence 0.73 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2588654 Disease Relevance 0 Pain Relevance 0

CXCR4 containing protein complexes were isolated using Protein G agarose beads and then separated by denaturing, reducing SDS electrophoresis.

Localization (separated) of CXCR4

11) Confidence 0.73 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2588654 Disease Relevance 0.05 Pain Relevance 0

CXCR4 and MIF are co-localized in cells in the urothelium and CYP induced co-localization of CXCR4 and MIF to superficial cells of the urothelium.

Localization (localization) of CXCR4

12) Confidence 0.73 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2588654 Disease Relevance 0.64 Pain Relevance 0.52

Following CYP-treatment, however, there was focal redistribution of CXCR4 immunostaining with superficial cells (and especially at their apical ends) showing moderate patchy staining (Fig 2C,D), while basal and intermediate cells appear to decrease in staining intensity.

Localization (redistribution) of CXCR4 in apical ends

13) Confidence 0.73 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2588654 Disease Relevance 0.06 Pain Relevance 0

Figure 3 shows representative bladder sections from each group immunostained for MIF (FITC color), CXCR4 (TRITC color) and an overlay of those two panels (co-localization indicated by orange color; nuclear staining by DAPI shown in blue).

Localization (localization) of CXCR4 in bladder

14) Confidence 0.69 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2588654 Disease Relevance 0 Pain Relevance 0

Co-immunoprecipitations studied MIF-CXCR4 associations.Urothelial basal and intermediate (but not superficial) cells in saline-treated rats contained CXCR4, co-localized with MIF.

Localization (localized) of CXCR4

15) Confidence 0.69 Published 2008 Journal PLoS ONE Section Abstract Doc Link PMC2588654 Disease Relevance 0.43 Pain Relevance 0.18

Colocalization of CXCR4 and either IB4 or TRPV1 was limited to only 3.8 ± 0.3% or 3.9 ± 0.13% of the total neurons counted respectively (Fig. 5A, D, G).

Localization (Colocalization) of CXCR4 in IB4

16) Confidence 0.63 Published 2009 Journal Mol Pain Section Body Doc Link PMC2734548 Disease Relevance 0.20 Pain Relevance 0.12

In addition, some G-protein coupled receptors, including the closely related CXCR4 receptor, have been shown to be present in the nucleus as well as on the plasma membrane, where they are thought to activate nuclear effects through additional pathways (for review, see [36]).

Localization (present) of CXCR4 receptor in plasma

17) Confidence 0.08 Published 2008 Journal Mol Pain Section Body Doc Link PMC2562993 Disease Relevance 0.05 Pain Relevance 0.08

General Comments

This test has worked.