INT174339

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Context Info
Confidence 0.61
First Reported 2003
Last Reported 2010
Negated 0
Speculated 2
Reported most in Body
Documents 7
Total Number 23
Disease Relevance 8.27
Pain Relevance 4.95

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

isomerase activity (Mif) cell proliferation (Mif) extracellular space (Mif)
aging (Mif) extracellular region (Mif) nucleus (Mif)
Anatomy Link Frequency
urothelial cells 8
urine 8
macrophage 6
bladder 6
lumen 4
Mif (Rattus norvegicus)
Pain Link Frequency Relevance Heat
Inflammatory stimuli 88 99.98 Very High Very High Very High
substance P 75 99.98 Very High Very High Very High
Inflammation 520 99.92 Very High Very High Very High
agonist 129 99.90 Very High Very High Very High
Spinal cord 21 98.16 Very High Very High Very High
cytokine 134 97.32 Very High Very High Very High
lidocaine 153 91.28 High High
ischemia 69 88.00 High High
Dorsal horn 10 87.12 High High
interstitial cystitis 51 85.12 High High
Disease Link Frequency Relevance Heat
INFLAMMATION 593 99.92 Very High Very High Very High
Peptic Ulcer 1 99.20 Very High Very High Very High
Cancer 117 98.72 Very High Very High Very High
Necrosis 5 98.48 Very High Very High Very High
Colitis 1 98.48 Very High Very High Very High
Frailty 1 98.16 Very High Very High Very High
Cystitis 104 97.72 Very High Very High Very High
Disease 13 89.20 High High
Cv Unclassified Under Development 69 88.00 High High
Sepsis 6 87.04 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Stimulating UROtsa cells with 100 nM thrombin significantly increased the amount of MIF released into the culture media when compared to vehicle control (sterile saline: 65.17.4 ng MIF/ml; thrombin: 203.914.6; p0.001).
Positive_regulation (increased) of Localization (released) of MIF
1) Confidence 0.61 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3013117 Disease Relevance 0 Pain Relevance 0
Figure 3A shows that thrombin stimulation in the range of 10 nM to 200 nM increased MIF released into the culture media in a concentration-dependent manner.
Positive_regulation (increased) of Localization (released) of MIF
2) Confidence 0.61 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3013117 Disease Relevance 0 Pain Relevance 0
Inflammatory stimuli elicit MIF release from the urothelium into the bladder lumen and upregulation of MIF expression by the bladder in general and urothelium in particular [8], [9].
Positive_regulation (elicit) of Localization (release) of MIF in lumen associated with inflammatory stimuli
3) Confidence 0.53 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3013117 Disease Relevance 0.56 Pain Relevance 0.36
This raises the possibility that these cells will be activated by MIF present in the urine and in fact, CYP (present study) and other inflammatory stimuli [8]–[10] increase luminal MIF release.
Positive_regulation (increase) of Localization (release) of MIF in urine associated with inflammatory stimuli
4) Confidence 0.48 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2588654 Disease Relevance 0.37 Pain Relevance 0.23
MIF is upregulated in neurons in the brain and released into the CSF following intracisternal LPS or spinal cord injury [7,21].
Positive_regulation (upregulated) of Localization (released) of MIF in brain associated with spinal cord
5) Confidence 0.47 Published 2003 Journal BMC Neurosci Section Body Doc Link PMC184455 Disease Relevance 0.65 Pain Relevance 0.54
Heat-inactivated thrombin was ineffective in stimulating MIF release from UROtsa cells which argues against this possibility.
Positive_regulation (stimulating) of Localization (release) of MIF
6) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3013117 Disease Relevance 0.05 Pain Relevance 0
Our results thus confirm earlier findings of thrombin-induced MIF release from human endothelial cells [17] and we extend those results by showing that the same phenomenon occurs in vivo.
Positive_regulation (induced) of Localization (release) of MIF in endothelial cells
7) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3013117 Disease Relevance 0 Pain Relevance 0
Inflammatory stimuli elicit MIF release from the urothelium into the bladder lumen and upregulation of MIF expression by the bladder in general and urothelium in particular [8], [9].
Positive_regulation (upregulation) of Localization (release) of MIF in lumen associated with inflammatory stimuli
8) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3013117 Disease Relevance 0.63 Pain Relevance 0.37
We investigated the effect of stimulation with thrombin, a Protease Activated Receptor-1 (PAR1) agonist, on MIF release and MIF mRNA upregulation in urothelial cells.


Positive_regulation (upregulation) of Localization (release) of MIF in urothelial cells associated with agonist
9) Confidence 0.44 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC3013117 Disease Relevance 0.28 Pain Relevance 0.24
We cannot rule out a contribution of renal or ureteral MIF release to increased urine MIF levels observed in this study after CYP-treatment, Yet our current findings of increased urine MIF with concomitant decrease in bladder MIF protein levels are consistent with earlier findings where, in animals with bladders isolated from the kidneys (thus removing potential renal and ureteral contributions), we observed similar results [7], [9]).
Positive_regulation (increased) of Localization (release) of MIF in urine
10) Confidence 0.42 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2588654 Disease Relevance 0.42 Pain Relevance 0.25
Therefore, release of urothelial preformed MIF and activation of MIF production in the bladder (and urothelium in particular) by inflammatory stimuli are key elements in MIF-mediated bladder inflammation.
Positive_regulation (activation) of Localization (release) of MIF in bladder associated with inflammation and inflammatory stimuli
11) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3013117 Disease Relevance 0.72 Pain Relevance 0.41
Our current results suggest that one component of PAR1-mediated bladder inflammation may be release of MIF from urothelial cells and MIF upregulation.
Positive_regulation (upregulation) of Localization (release) of MIF in bladder associated with inflammation
12) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3013117 Disease Relevance 1.23 Pain Relevance 0.72
Although local thrombin formation during inflammation is likely to occur in the suburothelial compartment and thus stimulate basal and intermediate cells to elicit MIF release, our findings suggest that proteases present in the urine may also be able to activate PAR1 receptors in the urothelium, elicit MIF release and thus contribute to the initiation or maintenance of cystitis.
Positive_regulation (activate) of Localization (release) of MIF in urine associated with inflammation and cystitis
13) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3013117 Disease Relevance 0.42 Pain Relevance 0.21
We also document that thrombin stimulation of urothelial cells, whether in vitro (using UROtsa cells) or in vivo (using intravesical thrombin application in rats) results in MIF release, and this effect occurs quickly after thrombin application (15 min in vitro).
Spec (whether) Positive_regulation (results) of Localization (release) of MIF in urothelial cells
14) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3013117 Disease Relevance 0.06 Pain Relevance 0
Activation of urothelial PAR1 receptors, either by locally generated thrombin or proteases present in the urine, may mediate bladder inflammation by inducing urothelial MIF release and upregulating urothelial MIF expression.



Positive_regulation (inducing) of Localization (release) of MIF in urine associated with inflammation
15) Confidence 0.36 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC3013117 Disease Relevance 0.10 Pain Relevance 0.28
Therefore, as part of our investigation of MIF-mediated bladder inflammation, we examined whether: 1) Transformed normal human urothelial cells expressed PAR receptors in general, and PAR1 receptor specifically and also whether they express MIF; 2) the location of PAR1 receptors (since it had not been described) and MIF in rat urothelium; 3) whether thrombin stimulation elicits MIF release from human urothelial cells in vitro and from rat urothelial cells in vivo and 4) whether thrombin stimulation elicits MIF upregulation in human urothelial cells in vitro and from rat urothelial cells in vivo.


Spec (whether) Positive_regulation (elicits) of Spec (whether) Localization (release) of MIF in urothelial cells associated with inflammation
16) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3013117 Disease Relevance 0.24 Pain Relevance 0.12
Thrombin stimulation of urothelial cells resulted in a concentration- and time-dependent increase in MIF release both in vitro (UROtsa; 2.8-fold increase at 1 hr) and in vivo (rat; 4.5-fold) while heat-inactivated thrombin had no effect.
Positive_regulation (increase) of Localization (release) of MIF in urothelial cells
17) Confidence 0.36 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC3013117 Disease Relevance 0.05 Pain Relevance 0.29
We showed previously that substance P elicits MIF release from the bladder in general, and urothelium in particular, dependent on bladder nerve activation [9], [10], [24].
Positive_regulation (elicits) of Localization (release) of MIF in bladder associated with substance p
18) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3013117 Disease Relevance 0.82 Pain Relevance 0.57
Finally, while endotoxin can elicit MIF release it also results in MIF down-regulation [26], [33] which is opposite to the effect of up-regulation seen in our studies.
Positive_regulation (elicit) of Localization (release) of MIF
19) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3013117 Disease Relevance 0 Pain Relevance 0
Since thrombin contained a small amount of endotoxin and because endotoxin can elicit MIF release [26], it was possible that our thrombin results were due to endotoxin contamination.
Positive_regulation (elicit) of Localization (release) of MIF
20) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3013117 Disease Relevance 0.06 Pain Relevance 0

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