INT162368

Context Info Confidence 0.42 First Reported 2009 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 17 Total Number 18 Disease Relevance 7.96 Pain Relevance 3.34

signal transduction (Map3k8) cell cycle (Map3k8) kinase activity (Map3k8) cytoplasm (Map3k8)

Anatomy Link Frequency adipocytes 2 macrophage 1 Map3k8 (Mus musculus)

Pain Link Frequency Relevance Heat imagery 1 99.08 cytokine 512 99.00 Inflammation 354 98.56 rheumatoid arthritis 2 98.28 Pain 53 96.44 Acupuncture 42 95.36 Kinase C 13 84.08 Inflammatory stimuli 65 78.96 Inflammatory mediators 26 78.88 chemokine 3 75.68

Disease Link Frequency Relevance Heat Obesity 1378 99.64 INFLAMMATION 444 98.56 Rheumatoid Arthritis 2 98.28 Pain 66 96.44 Disease 17 96.40 Autoimmune Disease 2 95.44 Peritonitis 1 93.16 Diabetes Mellitus 104 90.48 Insulin Resistance 130 84.88 Targeted Disruption 13 74.88

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Accordingly, Cot/tpl2 deficiency provoked a 25-30% reduction in luminol-mediated bioluminescence and neutrophil recruitment together with a 65% lower macrophage recruitment 4 h following zymosan-induced peritonitis.

Negative_regulation (deficiency) of Cot/tpl2 in macrophage associated with peritonitis

1) Confidence 0.42 Published 2010 Journal J. Biol. Chem. Section Abstract Doc Link 20736176 Disease Relevance 0.46 Pain Relevance 0.35

We showed that inhibition of Tpl2 markedly reduced IL-1?

Negative_regulation (inhibition) of Tpl2

2) Confidence 0.42 Published 2010 Journal Diabetes Section Body Doc Link PMC2797946 Disease Relevance 0.32 Pain Relevance 0.09

This review will describe the physiological regulation and importance of Cot/Tpl-2 in inflammation as well as the landscape of small molecules that have been reported as Cot/Tpl-2 inhibitors.

Negative_regulation (inhibitors) of Cot/Tpl-2 associated with inflammation

3) Confidence 0.42 Published 2009 Journal Curr Top Med Chem Section Abstract Doc Link 19689369 Disease Relevance 0.67 Pain Relevance 0.33

By inference, pharmaceutical agents that inhibit Cot/Tpl-2 kinase have the potential to be novel and effective therapies for the treatment of these diseases.

Negative_regulation (inhibit) of Cot/Tpl-2 associated with disease

4) Confidence 0.41 Published 2009 Journal Curr Top Med Chem Section Abstract Doc Link 19689369 Disease Relevance 0.71 Pain Relevance 0.36

However, Tpl2 inhibition did not totally block the lipolytic effect of TNF-?

Negative_regulation (inhibition) of Tpl2

5) Confidence 0.31 Published 2010 Journal Diabetes Section Body Doc Link PMC2797946 Disease Relevance 0.55 Pain Relevance 0.28

Transfection of siRNA against Tpl2 achieved >80% efficiency in reducing endogenous Tpl2 protein levels (Fig. 4A).

Negative_regulation (reducing) of Tpl2 protein

6) Confidence 0.31 Published 2010 Journal Diabetes Section Body Doc Link PMC2797946 Disease Relevance 0.22 Pain Relevance 0.25

Tpl2 inhibitor acts as a potent, reversible, and ATP-competitive inhibitor of Tpl2 with an IC50 of 50 nmol/l.

Negative_regulation (inhibitor) of Tpl2

7) Confidence 0.31 Published 2010 Journal Diabetes Section Body Doc Link PMC2797946 Disease Relevance 0.50 Pain Relevance 0.14

In human adipocytes, pharmacological inhibition of Tpl2 also inhibited ERK1/2 activation induced by IL-1?

Negative_regulation (inhibition) of Tpl2 in adipocytes associated with obesity

8) Confidence 0.31 Published 2010 Journal Diabetes Section Body Doc Link PMC2797946 Disease Relevance 0.27 Pain Relevance 0.10

Tpl2 inhibitor acts as a potent, reversible, and ATP-competitive inhibitor of Tpl2 with an IC50 of 50 nmol/l.

Negative_regulation (inhibitor) of Tpl2

9) Confidence 0.31 Published 2010 Journal Diabetes Section Body Doc Link PMC2797946 Disease Relevance 0.58 Pain Relevance 0.17

in adipocytes nearly suppressed the cytokine-induced MEK or ERK1/2 phosphorylation, whereas after inhibition of Tpl2, some phosphorylation remained.

Negative_regulation (inhibition) of Tpl2 in adipocytes associated with obesity and cytokine

10) Confidence 0.31 Published 2010 Journal Diabetes Section Body Doc Link PMC2797946 Disease Relevance 0.43 Pain Relevance 0.11

Tpl2 inhibition markedly blunted the effects of IL-1?

Negative_regulation (inhibition) of Tpl2

11) Confidence 0.31 Published 2010 Journal Diabetes Section Body Doc Link PMC2797946 Disease Relevance 0.42 Pain Relevance 0.09

Furthermore, compared with Tpl2 inhibitors, drugs that inhibit IKK?

Negative_regulation (inhibitors) of Tpl2

12) Confidence 0.31 Published 2010 Journal Diabetes Section Body Doc Link PMC2797946 Disease Relevance 0.81 Pain Relevance 0.12

This could be because siRNA knockdown or pharmacological inhibition of Tpl2 was not sufficient to completely shutdown Tpl2 activity.

Negative_regulation (shutdown) of Tpl2

13) Confidence 0.31 Published 2010 Journal Diabetes Section Body Doc Link PMC2797946 Disease Relevance 0.53 Pain Relevance 0.22

treatment was strongly prevented when cells were pretreated with the Tpl2 inhibitor (Fig. 3D and E).

Negative_regulation (inhibitor) of Tpl2

14) Confidence 0.31 Published 2010 Journal Diabetes Section Body Doc Link PMC2797946 Disease Relevance 0.29 Pain Relevance 0.19

According to this pattern one were supposed to have reduced EST, (from 3 to 2), and three of them that were supposed to report increased EST, from 4 to 5 and 6 to 7 respectively, after EA as compared with before EA.

Negative_regulation (reduced) of EST

15) Confidence 0.30 Published 2010 Journal Chin Med Section Body Doc Link PMC2942886 Disease Relevance 0.06 Pain Relevance 0.11

Tpl2 knockdown markedly decreased MEK and ERK1/2 phosphorylation induced by IL-1?

Negative_regulation (knockdown) of Tpl2

16) Confidence 0.27 Published 2010 Journal Diabetes Section Body Doc Link PMC2797946 Disease Relevance 0.27 Pain Relevance 0.25

MEK inhibition by U0126 treatment slightly decreased basal lipolysis and inhibited cytokines effect to a level comparable to the effect observed following Tpl2 inhibition (Fig. 5A and B). siRNA-mediated silencing of Tpl2 also reduced IL-1?

Negative_regulation (inhibition) of Tpl2 associated with cytokine

17) Confidence 0.27 Published 2010 Journal Diabetes Section Body Doc Link PMC2797946 Disease Relevance 0.86 Pain Relevance 0.15

EST increase was reported by 5 (23%) of the 22 women, unchanged by 11 (50%) and a decreased EST by the remaining 6 (27%) women.

Negative_regulation (decreased) of EST

18) Confidence 0.22 Published 2010 Journal Chin Med Section Body Doc Link PMC2942886 Disease Relevance 0 Pain Relevance 0.04

General Comments

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