INT102548

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Context Info
Confidence 0.59
First Reported 2002
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 14
Total Number 23
Disease Relevance 19.84
Pain Relevance 7.22

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

cytosol (Ccr2) signal transduction (Ccr2) plasma membrane (Ccr2)
signal transducer activity (Ccr2)
Anatomy Link Frequency
monocytes 6
microglia 2
macrophages 1
peritoneal macrophage 1
THP-1 1
Ccr2 (Mus musculus)
Pain Link Frequency Relevance Heat
chemokine 219 100.00 Very High Very High Very High
cytokine 58 100.00 Very High Very High Very High
Pain 29 100.00 Very High Very High Very High
Dynorphin 2 100.00 Very High Very High Very High
antagonist 44 99.52 Very High Very High Very High
Inflammatory response 79 99.48 Very High Very High Very High
Spinal cord 43 99.28 Very High Very High Very High
Inflammation 575 99.20 Very High Very High Very High
Paracetamol 9 99.00 Very High Very High Very High
Multiple sclerosis 97 98.80 Very High Very High Very High
Disease Link Frequency Relevance Heat
Pain 18 100.00 Very High Very High Very High
Disease 206 99.92 Very High Very High Very High
Multiple Sclerosis 616 99.40 Very High Very High Very High
INFLAMMATION 674 99.28 Very High Very High Very High
Adhesions 56 99.24 Very High Very High Very High
Demyelinating Disease 83 98.80 Very High Very High Very High
Cancer 19 97.56 Very High Very High Very High
Alzheimer's Dementia 2 97.56 Very High Very High Very High
Neuropathic Pain 6 97.48 Very High Very High Very High
Influenza Virus Infection 246 97.40 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Mice deficient in both CCR2 and CX3CR1 (Ccr2RFP/RFPCx3cr1GFP/GFP mice) were included to probe the interactions between these receptors in EAE.
Negative_regulation (deficient) of CCR2 associated with multiple sclerosis
1) Confidence 0.59 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2965160 Disease Relevance 1.15 Pain Relevance 0.14
Because CCR2 is rapidly downregulated when monocytes differentiate into macrophages [33], these results suggest that the RFPhi cells were newly arrived monocyte/macrophages and show that the RFP and GFP markers are useful for tracking migrating monocytes.
Negative_regulation (downregulated) of CCR2 in monocytes
2) Confidence 0.59 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2965160 Disease Relevance 0.87 Pain Relevance 0.21
Loss of CCR2 was also found to alter acetaminophen-induced expression of tumor necrosis factor alpha, monocyte chemoattractant protein 3, and KC/gro.
Negative_regulation (Loss) of CCR2 in monocyte associated with necrosis, paracetamol and cancer
3) Confidence 0.58 Published 2002 Journal Hepatology Section Abstract Doc Link 11981759 Disease Relevance 0.78 Pain Relevance 0.91
We predicted that CCR2 deficiency would preferentially reduce Ly6Chi monocyte infiltration into the CNS of mice with EAE.
Negative_regulation (deficiency) of CCR2 in monocyte associated with multiple sclerosis
4) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2965160 Disease Relevance 1.15 Pain Relevance 0.13
Flow cytometric analysis of Ccr2RFP/+ and Ccr2RFP/RFP peripheral blood cells stained for cell-surface CCR2 (Figure 1C) confirmed bi-allelic expression of CCR2 and RFP in heterozygous mice and deletion of CCR2 in Ccr2RFP/RFP homozygous mice.
Negative_regulation (deletion) of CCR2 in blood cells
5) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2965160 Disease Relevance 0.17 Pain Relevance 0.03
CCR2 deficiency led to an increase in the number of neutrophils, from 8% to 16% of the total infiltrating cells (Figure 4D).
Negative_regulation (deficiency) of CCR2 in neutrophils
6) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2965160 Disease Relevance 0.40 Pain Relevance 0.07
Among inflammatory CD45hi cells, there were strikingly fewer CD115+ monocytes/macrophages in the absence of CCR2 (Figure 4D).
Negative_regulation (absence) of CCR2 in monocytes associated with inflammation
7) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2965160 Disease Relevance 0.54 Pain Relevance 0.09
These data explain the rapid antinociceptive effects of peripherally administered CCR2 antagonists under these circumstances, suggesting that CCR2 antagonists may ameliorate pain by inhibiting CCR2 receptor activation in the periphery.
Negative_regulation (inhibiting) of CCR2 associated with pain, antagonist and antinociceptive
8) Confidence 0.43 Published 2009 Journal J. Neurosci. Section Abstract Doc Link 19553445 Disease Relevance 0.83 Pain Relevance 0.81
By contrast, deletion of CCR2 in Ccr2RFP/RFPCx3cr1+/GFP mice drastically reduced peritoneal macrophage recruitment.
Negative_regulation (deletion) of CCR2 in peritoneal macrophage
9) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2965160 Disease Relevance 1.04 Pain Relevance 0.21
The delay in EAE development was presumably due to the absence of CCR2+ monocytes in the CNS.
Negative_regulation (absence) of CCR2 in monocytes associated with multiple sclerosis
10) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2965160 Disease Relevance 0.69 Pain Relevance 0.12
Monocyte recruitment was little affected by loss of the second CX3CR1 allele (Ccr2RFP/+Cx3cr1GFP/GFP), but was markedly reduced by loss of the second CCR2 allele (Ccr2RFP/RFPCx3cr1GFP/+) (Figure 3B).
Negative_regulation (loss) of CCR2 in Monocyte
11) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2965160 Disease Relevance 0.37 Pain Relevance 0.03
CCR2 deficiency leads to lower microglia accumulation and higher brain beta-amyloid (Abeta) levels, indicating that early microglial accumulation promotes Abeta clearance.
Negative_regulation (deficiency) of CCR2 in microglia associated with alzheimer's dementia and abeta
12) Confidence 0.41 Published 2008 Journal Trends Pharmacol. Sci. Section Abstract Doc Link 18835047 Disease Relevance 1.01 Pain Relevance 0.33
These include a decrease in glial activity (astrocytes and microglial cells) as well as pain mediators such as dynorphin, COX-2 and chemotactic cytokine receptor (CCR2).
Negative_regulation (decrease) of CCR2 in microglial cells associated with pain, dynorphin and cytokine
13) Confidence 0.37 Published 2006 Journal Pain Section Abstract Doc Link 16360279 Disease Relevance 1.08 Pain Relevance 0.95
Thus, while the PPAR-gamma agonist, pioglitazone, significantly attenuated exaggerated inflammatory responses in smoke-exposed mice, a CCR2 deficiency did not appear to confer any beneficial effect on smoke-exposed influenza-infected animals.


Negative_regulation (deficiency) of CCR2 associated with inflammatory response, influenza virus infection and agonist
14) Confidence 0.35 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2953496 Disease Relevance 1.15 Pain Relevance 0.20
Interestingly, complete absence of the CCR2 receptor did not attenuate the exaggerated inflammation observed in the BAL of smoke-exposed influenza-infected animals (Figure 6A).
Negative_regulation (absence) of CCR2 receptor associated with inflammation and influenza virus infection
15) Confidence 0.35 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2953496 Disease Relevance 0.96 Pain Relevance 0.30
Blocking of the CCL2-CCR2 axis with neutralizing antibodies limits the development of subsequent relapses [54].
Negative_regulation (Blocking) of CCR2 associated with recurrence
16) Confidence 0.32 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2596102 Disease Relevance 1.10 Pain Relevance 0.34
Further mechanistic evaluation revealed that a deficiency in CCR2 did not improve the inflammatory outcome in smoke-exposed, virally-infected animals.


Negative_regulation (deficiency) of CCR2 associated with inflammation
17) Confidence 0.31 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2953496 Disease Relevance 0.84 Pain Relevance 0.33
Jee et al [15] compared the histological features and MCP-1 (CCL2) and CCR2 expression levels in the lesions of Lewis rats during the acute attack of monophasic EAE and during the first two clinical events of CR-EAE.
Negative_regulation (compared) of CCR2 associated with multiple sclerosis
18) Confidence 0.28 Published 2005 Journal J Neuroinflammation Section Body Doc Link PMC554759 Disease Relevance 1.73 Pain Relevance 0.29
Development of atherosclerosis (induced by a variety of means) has been shown to be attenuated in mice made deficient in adhesion molecules like P- and E-selectins or deficient in the chemokine receptor CCR2 [2]–[5].
Negative_regulation (deficient) of CCR2 associated with chemokine, atherosclerosis and adhesions
19) Confidence 0.26 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2423484 Disease Relevance 1.49 Pain Relevance 0.13
Other inhibitors in clinical trial include the small molecule CCR2 inhibitors CCX915 (by ChemoCentryx) for multiple sclerosis (phase I), INCB3284 (by Incyte/Pfizer) which is in phase IIa for treatment of RA, and the monoclonal antibody ABN912 against CCL2 (by Novartis) for COPD (phase I) and RA (phase II).
Negative_regulation (inhibitors) of CCR2 associated with multiple sclerosis, pulmonary disease and rheumatoid arthritis
20) Confidence 0.16 Published 2007 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2695202 Disease Relevance 0.79 Pain Relevance 0.33

General Comments

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