INT244490

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Context Info
Confidence 0.33
First Reported 2008
Last Reported 2010
Negated 1
Speculated 2
Reported most in Body
Documents 4
Total Number 46
Disease Relevance 41.16
Pain Relevance 10.37

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

unfolded protein binding (HSP90B1) protein folding (HSP90B1) cytosol (HSP90B1)
endoplasmic reticulum (HSP90B1) RNA binding (HSP90B1) response to stress (HSP90B1)
Anatomy Link Frequency
epithelial cells 7
plasma 4
Intestine 3
brain 2
Caco-2 2
HSP90B1 (Homo sapiens)
Pain Link Frequency Relevance Heat
Crohn's disease 2193 99.84 Very High Very High Very High
rheumatoid arthritis 43 99.84 Very High Very High Very High
cytokine 134 99.56 Very High Very High Very High
Inflammation 229 98.22 Very High Very High Very High
chemokine 11 41.32 Quite Low
Nerve growth factor 1 18.00 Low Low
Central nervous system 21 16.28 Low Low
Inflammatory response 44 13.92 Low Low
abdominal pain 43 8.96 Low Low
Nicotine 9 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Stress 800 100.00 Very High Very High Very High
Cancer 169 100.00 Very High Very High Very High
Disease 2381 99.84 Very High Very High Very High
Rheumatoid Arthritis 43 99.84 Very High Very High Very High
Shock 44 99.72 Very High Very High Very High
Bacterial Infection 43 99.70 Very High Very High Very High
Escherichia Infection 43 99.56 Very High Very High Very High
Acquired Immune Deficiency Syndrome Or Hiv Infection 110 99.52 Very High Very High Very High
Inflammatory Bowel Disease 516 99.48 Very High Very High Very High
Adhesions 183 99.10 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The Gp96 expression level in the ileum from patients in the quiescent phase of CD was still increased compared with that in the ileum from controls.
Gene_expression (expression) of Gp96 in ileum associated with crohn's disease
1) Confidence 0.33 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 0.68 Pain Relevance 0.34
Such a co-localisation of Gp96 and CEACAM6 in patients with CD at the apical side of ileal epithelial cells is of great interest, since we previously reported that CEACAM6 acts as a receptor for E coli type 1 pili and therefore allows AIEC to colonise the ileal mucosa12 and promote gut inflammation as shown in transgenic CEABAC10 mice expressing the human CEACAM6 molecule.46 Increased expression of Gp96 at the same site as CEACAM6 should increase AIEC virulence, since the bacteria would be able to colonise the mucosa by binding to CEACAM6 and can better invade the ileal epithelium through AIEC OMV–Gp96 interaction.
Gene_expression (expression) of Gp96 in epithelial cells associated with targeted disruption, inflammation and crohn's disease
2) Confidence 0.33 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 0.54 Pain Relevance 0.17
As CEACAM6 is abnormally expressed in ileal mucosa of patients with CD12 and as the expression of Grp78, another ER-localised stress response chaperone, is also increased in inflamed ileal CD mucosa and in inflamed colonic UC and CD mucosa,23 29 we analysed the expression of Gp96, CEACAM6 and Grp78 in CD ileal and colonic specimens.
Spec (analysed) Gene_expression (expression) of Gp96 associated with stress, inflammatory bowel disease and crohn's disease
3) Confidence 0.33 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 1.30 Pain Relevance 0.47
Immunohistochemistry showed a very strong staining of Gp96 in the ileal epithelium of patients in the acute phase of CD, in contrast to control ileal biopsies that showed very weak or no Gp96 expression.
Neg (no) Gene_expression (expression) of Gp96 in epithelium associated with crohn's disease
4) Confidence 0.33 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 0.67 Pain Relevance 0.34
, we did not notice any modification of Gp96 expression.
Gene_expression (expression) of Gp96
5) Confidence 0.33 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 1.63 Pain Relevance 0.29
From this result and as demonstrated in the present study, the AIEC mostly associated with the ileal form of CD are able to take advantage of Gp96 overexpression, since we show here that Gp96 acts as a host cell receptor for AIEC invasion via OMVs rich in OmpA protein.
Gene_expression (overexpression) of Gp96 associated with crohn's disease
6) Confidence 0.33 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 0.70 Pain Relevance 0.27
We also investigated whether infection with AIEC pathogenic bacteria can interfere with Gp96 expression, but we did not observe any increase in response to AIEC infection.
Gene_expression (expression) of Gp96 associated with infection
7) Confidence 0.33 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 1.23 Pain Relevance 0.19
Gp96 expression supports LF82 invasion
Gene_expression (expression) of Gp96
8) Confidence 0.33 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 0.86 Pain Relevance 0.21
This latter observation is in good agreement with the fact that Gp96 was found to be highly expressed in patients in both acute and quiescent phases of CD.
Gene_expression (expressed) of Gp96 associated with crohn's disease
9) Confidence 0.33 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 1.55 Pain Relevance 0.28
Western blot analysis of total protein extracts from CD ileal specimens taken in involved areas and of controls showed a strong expression of Gp96 in five out of six CD ileal mucosa specimens and only one out of six ileal mucosa specimens of controls (figure 1D).


Gene_expression (expression) of Gp96 associated with crohn's disease
10) Confidence 0.33 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 1.41 Pain Relevance 0.47
Western blot analysis indicated that, unlike CEACAM6 increased expression under proinflammatory cytokine stimulation, similar Gp96 expression was observed in proinflammatory cytokine-stimulated or unstimulated Caco-2 cells (figure 2B).
Gene_expression (expression) of Gp96 in Caco-2 associated with cytokine
11) Confidence 0.33 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 1.08 Pain Relevance 0.33
In addition, we can speculate that increased expression of Gp96 in patients with CD could also contribute to an abnormal colonisation of the mucosa by other bacteria using Gp96 as a plasma membrane receptor allowing the bacteria to bind to or to enter inside host cells, as already reported for L monocytogenes.21
Gene_expression (expression) of Gp96 in plasma associated with crohn's disease
12) Confidence 0.33 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 0.61 Pain Relevance 0.22
We hypothesise that patients at high risk for developing severe ileal CD are those who, in addition to expressing CEACAM6,12 overexpress Gp96 in the ileal mucosa.
Gene_expression (overexpress) of Gp96 associated with crohn's disease
13) Confidence 0.29 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 0.61 Pain Relevance 0.24
In conclusion, our findings highlight increased expression of the ER-localised stress response protein Gp96 in ileal epithelial cells of patients with CD.
Gene_expression (expression) of Gp96 in epithelial cells associated with stress and crohn's disease
14) Confidence 0.29 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 0.65 Pain Relevance 0.24
As shown in figure 1C, very strong staining of Gp96 was observed together with that of Grp78 and of CEACAM6 at the apical plasma membrane of the ileal epithelium of patients with CD.
Gene_expression (staining) of Gp96 in plasma associated with crohn's disease
15) Confidence 0.29 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 1.31 Pain Relevance 0.47
No fusion event of OMVs with the host cell membrane was observed when experiments were performed with Intestine-407 cells transfected with gp96 siRNA (data not shown) or with LF82-?
Gene_expression (transfected) of gp96 in Intestine
16) Confidence 0.29 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 0.39 Pain Relevance 0.10
ompA mutant, suggesting the need for an interaction between the eukaryotic Gp96 receptor and the bacterial OmpA protein from AIEC OMVs for fusion of vesicles with IECs and delivery into host cells of virulence factors that contribute to the invasion process.
Gene_expression (receptor) of Gp96 in vesicles
17) Confidence 0.29 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 0.33 Pain Relevance 0.07
Gp96 has already been reported to be a key mediator of the innate immune response due to its ability to bind pathogenic bacteria or their products.19–21 37 38 Indeed, Gp96 is a plasma membrane receptor for Vip, a Listeria monocytogenes virulence factor that is required for cell invasion and downstream signalling events.21 In addition, a Gp96 homologue, Ecgp96, the expression of which is increased during meningitis-associated E coli K1 infection of human BMECs, promotes invasion of these pathogenic bacteria.19 20 37
Gene_expression (homologue) of Gp96 in plasma associated with meningitis and infection
18) Confidence 0.29 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 0.61 Pain Relevance 0.03
In addition, in the presence of anti-Gp96 antibodies, LF82 OMVs were unable to restore the invasive defect of the LF82-?
Gene_expression (antibodies) of Gp96
19) Confidence 0.29 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 0.29 Pain Relevance 0.03
Gp96 protein expression is strongly increased in the ileal intestinal epithelium of patients with CD
Gene_expression (expression) of Gp96 in intestinal epithelium associated with crohn's disease
20) Confidence 0.26 Published 2010 Journal Gut Section Body Doc Link PMC2976078 Disease Relevance 0.33 Pain Relevance 0.16

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