INT169533

Context Info Confidence 0.68 First Reported 2006 Last Reported 2010 Negated 2 Speculated 0 Reported most in Body Documents 16 Total Number 21 Disease Relevance 8.62 Pain Relevance 2.14

transport (Cybb) mitochondrion (Cybb) oxidoreductase activity (Cybb) Golgi apparatus (Cybb) endoplasmic reticulum (Cybb) plasma membrane (Cybb)

Anatomy Link Frequency brain 12 neurons 6 inhibitory interneurons 2 central nervous system 2 dorsal horn 2 Cybb (Mus musculus)

Pain Link Frequency Relevance Heat Stimulus evoked pain 1 99.92 Dorsal horn 1 99.84 Central nervous system 13 99.08 cva 18 98.80 GABAergic 108 98.36 Spinal cord 4 97.60 imagery 72 96.08 ketamine 48 93.88 Nerve growth factor 1 93.40 cytokine 129 93.04

Disease Link Frequency Relevance Heat Brain Injury 318 99.96 Hypersensitivity 1 99.92 Aging 277 99.52 Apoptosis 153 99.52 Cv General 4 Under Development 12 99.36 Pain 1 99.24 Nervous System Injury 4 96.80 Mycobacterial Infection 141 95.20 Injury 32 93.52 Contusions 30 92.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Some recent studies have demonstrated that expression of gp91phox increases in brain after intracerebral hemorrhage, resulting in enhanced lipid peroxidation [24,41].

Positive_regulation (increases) of Gene_expression (expression) of gp91phox in brain associated with cv general 4 under development and cva

1) Confidence 0.68 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2917406 Disease Relevance 0.86 Pain Relevance 0.23

Consistent with a direct effect of IL-6 on Nox2 expression, direct systemic injection of IL-6 into mice increased Nox2 protein and activity, confirming the ability of peripheral IL-6 to mediate increased Nox2 expression and superoxide production in brain.

Positive_regulation (increased) of Gene_expression (expression) of Nox2 in brain

2) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2678193 Disease Relevance 0.20 Pain Relevance 0.05

Increased Nox2 protein expression in brain of aged animals is attenuated in IL-6-/- mice

Positive_regulation (Increased) of Gene_expression (expression) of Nox2 protein in brain

3) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2678193 Disease Relevance 0.38 Pain Relevance 0.06

IL-6-/- mice lack the age-related increase in Nox2 expression and superoxide production observed in old wild-type mice.

Positive_regulation (increase) of Gene_expression (expression) of Nox2

4) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2678193 Disease Relevance 0.05 Pain Relevance 0.03

In the context of chronically elevated peripheral IL-6 in aged animals, on the other hand, we wished to determine whether aging was associated with an increase in Nox2 expression in brain, by analyzing Nox2 protein expression in young (4 month old) and old (24 month old) mouse brain.

Positive_regulation (increase) of Gene_expression (expression) of Nox2 in brain associated with aging

5) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2678193 Disease Relevance 0.18 Pain Relevance 0.04

The robust induction of Nox2 expression and activity we observed led us to ask whether PV inhibitory interneurons might also be selectively lost during aging, as well.

Positive_regulation (induction) of Gene_expression (expression) of Nox2 in inhibitory interneurons associated with aging

6) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2678193 Disease Relevance 0.26 Pain Relevance 0.26

More importantly, direct application of IL-6 to cultured neurons resulted in a significant increase in Nox-2 expression and superoxide production which was fully blocked by the NF?

Positive_regulation (increase) of Gene_expression (expression) of Nox-2 in neurons

7) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2678193 Disease Relevance 0.16 Pain Relevance 0.12

B signaling can directly induce Nox2 expression in neurons.

Positive_regulation (induce) of Gene_expression (expression) of Nox2 in neurons

8) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2678193 Disease Relevance 0.32 Pain Relevance 0.07

Moreover, we recently demonstrated that IL-6 can directly induce and activate Nox2 protein expression in cultured neurons[15], but in that study in young mice, acute peripheral injection of IL-6 failed to induce brain Nox2 expression.

Neg (failed) Positive_regulation (induce) of Gene_expression (expression) of Nox2 in brain

9) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2678193 Disease Relevance 0.23 Pain Relevance 0.03

To quantify the age-related increase in Nox2 expression, and assess whether IL-6 was involved in this process, we determined levels of Nox2 protein in young and old wild-type (C57BL/6) and IL-6-deficient (IL-6-/-) animals.

Positive_regulation (increase) of Gene_expression (expression) of Nox2

10) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2678193 Disease Relevance 0.12 Pain Relevance 0.04

Gp91phox gene deletion reduces 3-NT generation after TBI in vivo

Positive_regulation (deletion) of Gene_expression (deletion) of Gp91phox associated with brain injury

11) Confidence 0.49 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2917406 Disease Relevance 0.58 Pain Relevance 0

Gp91phox gene deletion reduces 3-NT generation after TBI in vivo

Positive_regulation (after) of Gene_expression (deletion) of Gp91phox associated with brain injury

12) Confidence 0.49 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2917406 Disease Relevance 0.58 Pain Relevance 0

More importantly, direct application of IL-6 to cultured neurons resulted in a significant increase in Nox-2 expression and superoxide production which was fully blocked by the NF?

Positive_regulation (increase) of Gene_expression (expression) of Nox-2 in neurons

13) Confidence 0.47 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2678193 Disease Relevance 0.16 Pain Relevance 0.12

, BV-2 cells had increased inducible nitric oxide synthase and nitric oxide levels, consistent with a classical activated phenotype, and drastically increased expression of gp91phox.

Positive_regulation (increased) of Gene_expression (expression) of gp91phox

14) Confidence 0.45 Published 2010 Journal J Neuroinflammation Section Abstract Doc Link PMC2917406 Disease Relevance 0.62 Pain Relevance 0

Protein levels of gp91phox were not increased after TBI in the contralateral hemisphere of Wt mice.

Neg (not) Positive_regulation (increased) of Gene_expression (levels) of gp91phox associated with brain injury

15) Confidence 0.45 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2917406 Disease Relevance 0.73 Pain Relevance 0

Gp91phox expression increased mainly in amoeboid-shaped microglial cells of the ipsilateral hemisphere of Wt mice after TBI.

Positive_regulation (increased) of Gene_expression (expression) of Gp91phox in microglial cells associated with brain injury

16) Confidence 0.45 Published 2010 Journal J Neuroinflammation Section Abstract Doc Link PMC2917406 Disease Relevance 0.77 Pain Relevance 0

Repeated intraperitoneal injection of IL-6 (5 µg/kg i.p. every 12 hours times 3) in mice significantly increased expression of Nox2 protein in brain (Fig. 2d, top) and resulted in substantially higher superoxide levels, as documented by DHE oxidation (Fig. 2d, bottom).

Positive_regulation (increased) of Gene_expression (expression) of Nox2 protein in brain

17) Confidence 0.44 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2678193 Disease Relevance 0.07 Pain Relevance 0.03

Nox2 expression was induced in dorsal horn microglia immediately after L5 spinal nerve transection (SNT).

Positive_regulation (induced) of Gene_expression (expression) of Nox2 in dorsal horn associated with dorsal horn

18) Confidence 0.42 Published 2010 Journal Proc. Natl. Acad. Sci. U.S.A. Section Abstract Doc Link 20679217 Disease Relevance 0.90 Pain Relevance 0.92

We then evaluated synaptosomes prepared from young and old IL-6-/- mice, and found that compared to old wild-type controls, IL-6-/- mice had an attenuation of age-induced increases in Nox2 O2 consumption (Fig. 3a, (F(1,6)?

Positive_regulation (increases) of Gene_expression (consumption) of Nox2

19) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2678193 Disease Relevance 0 Pain Relevance 0

In the central nervous system, Noh and Koh (2000) were able to demonstrate increased NADPH oxidase-derived (NOX2) ROS production in cortical cultures in response to zinc exposure [72].

Positive_regulation (increased) of Gene_expression (production) of NOX2 in central nervous system associated with central nervous system

20) Confidence 0.23 Published 2006 Journal J Neuroinflammation Section Body Doc Link PMC1637099 Disease Relevance 0.35 Pain Relevance 0.14

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