INT142607

Context Info Confidence 0.62 First Reported 2005 Last Reported 2010 Negated 0 Speculated 1 Reported most in Body Documents 41 Total Number 42 Disease Relevance 13.85 Pain Relevance 5.51

extracellular space (Cd40) extracellular region (Cd40) plasma membrane (Cd40) enzyme binding (Cd40)

Anatomy Link Frequency microglial cells 14 CD86 14 T cells 10 bone marrow 4 macrophages 3 Cd40 (Mus musculus)

Pain Link Frequency Relevance Heat agonist 229 99.98 Pain 19 99.16 Neuropeptide 10 98.80 Cannabinoid receptor 50 98.68 cytokine 254 97.60 Inflammation 359 97.18 aspirin 41 94.00 Arthritis 103 93.28 Inflammatory response 21 87.64 rheumatoid arthritis 62 87.20

Disease Link Frequency Relevance Heat Eye Disease 63 99.80 Influenza Virus Infection 81 99.70 Infection 131 99.50 Sprains And Strains 37 99.50 Drug Induced Neurotoxicity 10 99.36 Pain 19 99.16 Mixed Connective Tissue Disorder 70 99.06 Fatigue 15 99.00 Disease 398 97.60 INFLAMMATION 415 97.18

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Event

Anatomy

Negation

Speculation

Pain term

Disease term

peptide and enhanced CD40 expression on microglial cells derived from the Tg2576 mouse model of AD [28].

Positive_regulation (enhanced) of Gene_expression (expression) of CD40 in microglial cells associated with disease

1) Confidence 0.62 Published 2005 Journal J Neuroinflammation Section Body Doc Link PMC1352348 Disease Relevance 0.78 Pain Relevance 0.29

-induced CD40 expression in a dose-related manner (Figure. 1B).

Positive_regulation (induced) of Gene_expression (expression) of CD40

2) Confidence 0.62 Published 2005 Journal J Neuroinflammation Section Body Doc Link PMC1352348 Disease Relevance 0 Pain Relevance 0.09

signaling pathway to induce microglial CD40 expression and subsequent neurotoxicity [28].

Positive_regulation (induce) of Gene_expression (expression) of CD40 associated with drug induced neurotoxicity

3) Confidence 0.62 Published 2005 Journal J Neuroinflammation Section Body Doc Link PMC1352348 Disease Relevance 0.81 Pain Relevance 0.31

Our preliminary results from patients with uncharacteristic inflammatory disorders (n = 11, 8 females and 3 males), as defined by for example long-standing fatigue or pain, and no more specific diagnosis, show an elevated monocyte CD40 expression in most, but not all, cases (mean value 6 times higher than normal controls); an increased fraction of the CD14+ CD16+ monocyte subset (15% of all monocytes); and a most diverse T lymphocyte pattern.

Positive_regulation (elevated) of Gene_expression (expression) of CD40 in T lymphocyte associated with pain, inflammation and fatigue

4) Confidence 0.57 Published 2010 Journal BMC Infect Dis Section Body Doc Link PMC2912311 Disease Relevance 0.59 Pain Relevance 0.15

At Day 6 of culture, bone marrow-derived DCs from DBA/1 LacJ mice were transfected with CD40 siRNA or control siRNA.

Positive_regulation (transfected) of Gene_expression (transfected) of CD40 siRNA in bone marrow

5) Confidence 0.50 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875641 Disease Relevance 0 Pain Relevance 0

DCs were generated from bone marrow progenitors by standard IL-4 and GM-CSF culture and transfected on Day 6 with CD40-siRNA.

Positive_regulation (transfected) of Gene_expression (transfected) of CD40-siRNA in bone marrow

6) Confidence 0.50 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875641 Disease Relevance 0.27 Pain Relevance 0.08

To test this hypothesis, we used CD40-silenced DCs as allostimulators in MLR.

Positive_regulation (used) of Gene_expression (used) of CD40-silenced

7) Confidence 0.50 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875641 Disease Relevance 0.26 Pain Relevance 0.06

-induced CD40 expression in the immature murine DC cell line, BC1 (Iijima et al., 2003), and blocked the expression of high levels of surface molecules such as MHCs, B7-1, and B7-2 after lipopolysaccharide treatment in human DC (Nouri-Shirazi & Guinet, 2002).

Positive_regulation (induced) of Gene_expression (expression) of CD40

8) Confidence 0.49 Published 2010 Journal Anatomy & Cell Biology Section Body Doc Link PMC2998772 Disease Relevance 0 Pain Relevance 0

Amaya lparraguirre reported that although both influenza virus and CpG led to increased expression levels of costimulatory molecules on PDCs, including CD40 and CD86 as well as MHC II, an exception was CD80, which was expressed to the lower extend under the CpG stimuli than the influenza virus stimuli [38].

Positive_regulation (led) of Gene_expression (expression) of CD40 in CD86 associated with influenza virus infection

9) Confidence 0.46 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2793013 Disease Relevance 0.33 Pain Relevance 0

However, when combination of both E2 and CpG was used, the enhancements of CD40 and CD86 expression were more strikingly than CpG alone (Figure 2 and Figure S4).

Positive_regulation (enhancements) of Gene_expression (expression) of CD40 in CD86

10) Confidence 0.46 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2793013 Disease Relevance 0.14 Pain Relevance 0

-induced microglial CD40 expression do so by modification of the JAK/STAT pathway [34-39].

Positive_regulation (induced) of Gene_expression (expression) of CD40

11) Confidence 0.45 Published 2005 Journal J Neuroinflammation Section Body Doc Link PMC1352348 Disease Relevance 0.07 Pain Relevance 0.23

Furthermore, Western blotting examination consistently showed that JWH-015 co-treatment mitigates the inducible increase in CD40 protein expression in primary cultured microglial cells after IFN-?

Positive_regulation (increase) of Gene_expression (expression) of CD40 in microglial cells

12) Confidence 0.45 Published 2005 Journal J Neuroinflammation Section Body Doc Link PMC1352348 Disease Relevance 0 Pain Relevance 0.08

To examine the functional consequences of CB2 agonist treatment on CD40 expression, we stimulated mouse primary microglial cells with either IFN-?

Spec (examine) Positive_regulation (treatment) of Gene_expression (expression) of CD40 in microglial cells associated with agonist

13) Confidence 0.45 Published 2005 Journal J Neuroinflammation Section Body Doc Link PMC1352348 Disease Relevance 0.19 Pain Relevance 0.22

-induced microglial CD40 expression by opposing JAK/STAT1 pathway activation.

Positive_regulation (induced) of Gene_expression (expression) of CD40

14) Confidence 0.45 Published 2005 Journal J Neuroinflammation Section Body Doc Link PMC1352348 Disease Relevance 0.73 Pain Relevance 0.28

Flow cytometric analysis of microglial CD40 expression

Positive_regulation (microglial) of Gene_expression (expression) of CD40

15) Confidence 0.44 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2569027 Disease Relevance 0 Pain Relevance 0

, which consequently sensitizes the microglia by upregulating the expression of various immunoregulatory molecules, including CD40, on their cell surfaces [23,24].

Positive_regulation (upregulating) of Gene_expression (expression) of CD40 in microglia

16) Confidence 0.44 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2569027 Disease Relevance 0.93 Pain Relevance 0.25

-induced microglial CD40 expression [25,26].

Positive_regulation (induced) of Gene_expression (expression) of CD40

17) Confidence 0.44 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2569027 Disease Relevance 0.84 Pain Relevance 0.25

-induced CD40 expression in microglial cells

Positive_regulation (induced) of Gene_expression (expression) of CD40 in microglial cells

18) Confidence 0.42 Published 2005 Journal J Neuroinflammation Section Body Doc Link PMC1352348 Disease Relevance 0 Pain Relevance 0.04

-induced CD40 expression.

Positive_regulation (induced) of Gene_expression (expression) of CD40

19) Confidence 0.42 Published 2005 Journal J Neuroinflammation Section Abstract Doc Link PMC1352348 Disease Relevance 0.56 Pain Relevance 0.49

to potently induce microglial CD40 expression [28].

Positive_regulation (induce) of Gene_expression (expression) of CD40

20) Confidence 0.42 Published 2005 Journal J Neuroinflammation Section Body Doc Link PMC1352348 Disease Relevance 0.08 Pain Relevance 0.19

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