INT215096

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Context Info
Confidence 0.38
First Reported 2007
Last Reported 2010
Negated 0
Speculated 2
Reported most in Body
Documents 9
Total Number 12
Disease Relevance 11.61
Pain Relevance 1.61

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

cytoplasm (Hmgb1, Tlr2) cell morphogenesis (Hmgb1) intracellular (Tlr2)
DNA binding (Hmgb1) signal transduction (Tlr2) extracellular space (Hmgb1)
Anatomy Link Frequency
macrophage 2
bone marrow 2
GBM 1
urine 1
Hmgb1 (Mus musculus)
Tlr2 (Mus musculus)
Pain Link Frequency Relevance Heat
Inflammatory response 37 99.96 Very High Very High Very High
cytokine 178 99.64 Very High Very High Very High
Inflammation 225 95.24 Very High Very High Very High
Central nervous system 4 94.52 High High
ischemia 28 90.44 High High
fibrosis 80 78.64 Quite High
agonist 10 60.68 Quite High
antagonist 9 50.08 Quite High
rheumatoid arthritis 9 38.32 Quite Low
headache 4 25.00 Low Low
Disease Link Frequency Relevance Heat
Cancer 829 100.00 Very High Very High Very High
Hydronephrosis 154 100.00 Very High Very High Very High
Glioma 92 99.82 Very High Very High Very High
INFLAMMATION 252 99.76 Very High Very High Very High
Systemic Lupus Erythematosus 6 99.22 Very High Very High Very High
Glioblastoma 120 98.88 Very High Very High Very High
Injury 223 98.16 Very High Very High Very High
Ureteral Obstruction 72 97.88 Very High Very High Very High
Cv Unclassified Under Development 23 90.44 High High
Stress 17 90.04 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
We went further to identify glioma-derived HMGB1 as the endogenous TLR2 ligand, whose signaling is necessary to elicit systemic adaptive immune-mediated GBM regression and long-term immunological memory in an intracranial glioma model (Figure 11) [51,66].
HMGB1 Binding (ligand) of TLR2 in GBM associated with glioblastoma and glioma
1) Confidence 0.38 Published 2009 Journal PLoS Medicine Section Body Doc Link PMC2621261 Disease Relevance 1.23 Pain Relevance 0.04
Herein we uncovered a novel pathway for the activation of an effective anti-GBM immune response mediated by high-mobility-group box 1 (HMGB1), an alarmin protein released from dying tumor cells, which acts as an endogenous ligand for Toll-like receptor 2 (TLR2) signaling on bone marrow-derived GBM-infiltrating DCs.


HMGB1 Binding (ligand) of Toll-like receptor 2 in bone marrow associated with cancer and glioblastoma
2) Confidence 0.38 Published 2009 Journal PLoS Medicine Section Abstract Doc Link PMC2621261 Disease Relevance 1.23 Pain Relevance 0.05
Herein we uncovered a novel pathway for the activation of an effective anti-GBM immune response mediated by high-mobility-group box 1 (HMGB1), an alarmin protein released from dying tumor cells, which acts as an endogenous ligand for Toll-like receptor 2 (TLR2) signaling on bone marrow-derived GBM-infiltrating DCs.


HMGB1 Binding (ligand) of TLR2 in bone marrow associated with cancer and glioblastoma
3) Confidence 0.38 Published 2009 Journal PLoS Medicine Section Abstract Doc Link PMC2621261 Disease Relevance 1.29 Pain Relevance 0.05
Therefore, we hypothesized that HMGB1 could be an endogenous TLR2 ligand released from TK + GCV treated GL26 cells.
HMGB1 Binding (ligand) of TLR2
4) Confidence 0.38 Published 2009 Journal PLoS Medicine Section Body Doc Link PMC2621261 Disease Relevance 1.03 Pain Relevance 0.03
Indeed, fluorescence resonance energy transfer (FRET) analysis has demonstrated a close physical interaction between HMGB1 and TLR2 or TLR4 on macrophage cell surface within 5-15 minutes of HMGB1 incubation [47], long before subsequent HMGB1-induced cytokine release.
HMGB1 Binding (interaction) of TLR2 in macrophage associated with cytokine
5) Confidence 0.25 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2048740 Disease Relevance 0.30 Pain Relevance 0.26
Given the diverse range of receptors (e.g., TLR2, TLR4, or RAGE) involved in HMGB1 recognition [7], [50], [51], it is intriguing to investigate whether binding of HMGB1 to different receptors leads to combinational clustering of different receptors (such as TLR2 or TLR4) within the lipid rafts [38], [52], [53].
HMGB1 Spec (whether) Binding (binding) of TLR2
6) Confidence 0.25 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2048740 Disease Relevance 0.05 Pain Relevance 0.21
Indeed, fluorescence resonance energy transfer (FRET) analysis has demonstrated a close physical interaction between HMGB1 and TLR2 or TLR4 on macrophage cell surface within 5-15 minutes of HMGB1 incubation [47], long before subsequent HMGB1-induced cytokine release.
HMGB1 Binding (interaction) of TLR2 in macrophage associated with cytokine
7) Confidence 0.24 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2048740 Disease Relevance 0.30 Pain Relevance 0.25
Although cytoplasmic HMGB1 was only faintly found, it could as well interact with cytoplasmic TLR2.
HMGB1 Binding (interact) of TLR2 associated with hydronephrosis
8) Confidence 0.23 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682651 Disease Relevance 1.89 Pain Relevance 0.04
Moreover, there are data demonstrating that HMGB1 can be secreted from cells and can leak into the urine [34] making it possible to interact with apical TLR2.
HMGB1 Spec (possible) Binding (interact) of TLR2 in urine associated with hydronephrosis
9) Confidence 0.23 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682651 Disease Relevance 2.13 Pain Relevance 0.06
Autoantibodies against dsDNA and nucleosomes from SLE patients induce DC activation through TLR2 if bound to HMGB1 [89, 90].
HMGB1 Binding (bound) of TLR2 associated with systemic lupus erythematosus
10) Confidence 0.15 Published 2010 Journal Mediators of Inflammation Section Body Doc Link PMC2913853 Disease Relevance 0.15 Pain Relevance 0.03
Released in the extracellular compartment during acute inflammatory responses, HMGB1 also interact with TLR2 [21] and TLR9 [22].
HMGB1 Binding (interact) of TLR2 associated with inflammatory response
11) Confidence 0.08 Published 2010 Journal Gastroenterology Research and Practice Section Body Doc Link PMC2939438 Disease Relevance 1.08 Pain Relevance 0.28
Interactions of HMGB1 with TLR2 and TLR4 may provide an explanation for the ability of HMGB1 to generate inflammatory responses that are similar to those initiated by LPS [21].
HMGB1 Binding (Interactions) of TLR2 associated with inflammatory response
12) Confidence 0.07 Published 2010 Journal Gastroenterology Research and Practice Section Body Doc Link PMC2939438 Disease Relevance 0.92 Pain Relevance 0.31

General Comments

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