INT68653

Context Info Confidence 0.58 First Reported 1997 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 34 Total Number 35 Disease Relevance 14.27 Pain Relevance 6.56

cytosol (JUN) nucleoplasm (JUN) nuclear chromosome (JUN) aging (JUN) nucleus (JUN) DNA binding (JUN)

Anatomy Link Frequency colon 1 pore 1 phagocytes 1 blood 1 leukocytes 1 JUN (Homo sapiens)

Pain Link Frequency Relevance Heat Inflammation 93 100.00 Morphine 10 99.98 Inflammatory response 5 99.56 Spinal cord 6 99.52 Leflunomide 8 99.20 dexamethasone 11 98.94 Glutamate 3 98.56 cINOD 25 98.54 Paracetamol 21 98.44 opioid receptor 5 97.36

Disease Link Frequency Relevance Heat INFLAMMATION 113 100.00 Repression 19 100.00 Apoptosis 313 99.84 Toxicity 10 99.82 Cancer 118 99.80 Malignant Neoplastic Disease 20 98.46 Colon Cancer 26 98.28 Hyperplasia 6 95.92 Metastasis 60 95.28 Stress 18 94.72

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Sevoflurane-mediated suppression of AP-1 could be observed in primary CD3 lymphocytes from healthy volunteers, was time-dependent and concentration-dependent, and occurred at concentrations that are clinically achieved.

Negative_regulation (suppression) of AP-1 in lymphocytes

1) Confidence 0.58 Published 2004 Journal Anesthesiology Section Body Doc Link 15329596 Disease Relevance 0 Pain Relevance 0

Suppression of AP-1 was associated with altered phosphorylation of p38 mitogen-activated protein kinases.

Negative_regulation (Suppression) of AP-1

2) Confidence 0.58 Published 2004 Journal Anesthesiology Section Body Doc Link 15329596 Disease Relevance 0 Pain Relevance 0

CONCLUSION: The data demonstrate that sevoflurane is a specific inhibitor of AP-1 and may thus provide a molecular mechanism for the antiinflammatory effects associated with sevoflurane administration.

Negative_regulation (inhibitor) of AP-1

3) Confidence 0.58 Published 2004 Journal Anesthesiology Section Body Doc Link 15329596 Disease Relevance 0 Pain Relevance 0

The S phase block was accompanied by a reduction in the protein levels of cyclin A, cyclin B1, cyclin D1, cdc2, PCNA and the c-jun AP-1 component.

Negative_regulation (reduction) of AP-1

4) Confidence 0.57 Published 2003 Journal Int. J. Cancer Section Abstract Doc Link 14566835 Disease Relevance 0.53 Pain Relevance 0.06

Piroxicam selectively inhibits the growth of premalignant and malignant human oral cell lines by limiting their progression through the S phase and reducing the levels of cyclins and AP-1.

Negative_regulation (reducing) of AP-1 associated with malignant neoplastic disease

5) Confidence 0.57 Published 2003 Journal Int. J. Cancer Section Title Doc Link 14566835 Disease Relevance 0.60 Pain Relevance 0.10

Apoptosis was unaffected by inhibitors of the mitochondrial permeability transition pore and by inhibitors of Jun NH(2)-terminal kinases, p38 mitogen-activated protein kinase, or mitogen-activated protein kinase kinase 1/2.

Negative_regulation (inhibitors) of Jun in pore associated with apoptosis

6) Confidence 0.57 Published 2005 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 15665138 Disease Relevance 1.36 Pain Relevance 0.71

Overexpression of ICER in cultured spinal cord neurons results in the repression of the c-fos and c-jun promoters induced by forskolin and glutamate.

Negative_regulation (repression) of c-jun in spinal cord neurons associated with glutamate, repression and spinal cord

7) Confidence 0.57 Published 1997 Journal Eur. J. Neurosci. Section Abstract Doc Link 9517483 Disease Relevance 0.25 Pain Relevance 0.47

Exposure to naloxone before morphine treatment abolished morphine-induced inhibition of activator protein 1 activity in human blood monocytes and neutrophils.

Negative_regulation (inhibition) of activator protein 1 in monocytes

8) Confidence 0.51 Published 2007 Journal Eur J Anaesthesiol Section Body Doc Link 17583593 Disease Relevance 0 Pain Relevance 0

It resulted in an inhibition of AP-1-driven reporter gene activity and of the expression of the AP-1 target gene interleukin-3.

Negative_regulation (inhibition) of AP-1

9) Confidence 0.43 Published 2004 Journal Anesthesiology Section Body Doc Link 15329596 Disease Relevance 0 Pain Relevance 0

We report that in human colorectal carcinoma cells NSAIDs stimulated the three families of MAPK, extracellular regulated kinases, c-Jun N-terminal kinases, p38 MAPK and that this stimulation is prevented by N-acetyl cysteine.

Negative_regulation (prevented) of c-Jun associated with colon cancer and cinod

10) Confidence 0.41 Published 2002 Journal Biochem. Pharmacol. Section Abstract Doc Link 11841790 Disease Relevance 0.42 Pain Relevance 0.72

Recent studies indicated that mitochondrial permeability transition (mPT) plays a key role in APAP-induced toxicity and leflunomide (LEF) protects against the toxicity through inhibition of c-jun NH2-terminal protein kinase (JNK)-mediated pathway of mPT.

Negative_regulation (inhibition) of c-jun associated with toxicity, paracetamol and leflunomide

11) Confidence 0.41 Published 2008 Journal Toxicol. Lett. Section Abstract Doc Link 18588957 Disease Relevance 0.55 Pain Relevance 1.06

In fact, VEGF genes' expression is down-regulated by retinoids via the inhibition of the AP1 pathway [13].

Negative_regulation (inhibition) of AP1

12) Confidence 0.38 Published 2006 Journal Head Face Med Section Body Doc Link PMC1609104 Disease Relevance 0.26 Pain Relevance 0.04

The decrease in CD14 expression caused by morphine may play a role in inhibition of activator protein 1 activation following lipopolysaccharide treatment of phagocytes.

Negative_regulation (inhibition) of activator protein 1 in phagocytes

13) Confidence 0.37 Published 2007 Journal Eur J Anaesthesiol Section Body Doc Link 17583593 Disease Relevance 0 Pain Relevance 0

Morphine inhibits AP-1 activity and CD14 expression in leukocytes by a nitric oxide and opioid receptor-dependent mechanism.

Negative_regulation (inhibits) of AP-1 in leukocytes associated with opioid receptor and morphine

14) Confidence 0.37 Published 2007 Journal Eur J Anaesthesiol Section Title Doc Link 17583593 Disease Relevance 0 Pain Relevance 0.23

The inhibition of AP-1 and tumor promoter-induced transformation in JB6 cells occurs through a prostaglandin independent- and an Erk1- or Erk2-independent pathway.

Negative_regulation (inhibition) of AP-1 associated with cancer

15) Confidence 0.35 Published 1997 Journal J. Biol. Chem. Section Abstract Doc Link 9092536 Disease Relevance 0.74 Pain Relevance 0.42

The S phase block was accompanied by a reduction in the protein levels of cyclin A, cyclin B1, cyclin D1, cdc2, PCNA and the c-jun AP-1 component.

Negative_regulation (reduction) of c-jun

16) Confidence 0.35 Published 2003 Journal Int. J. Cancer Section Abstract Doc Link 14566835 Disease Relevance 0.53 Pain Relevance 0.06

RESULTS: Incubation of whole blood with morphine and subsequent stimulation with lipopolysaccharide decreased activator protein 1 nuclear content.

Negative_regulation (decreased) of activator protein 1 in blood

17) Confidence 0.33 Published 2007 Journal Eur J Anaesthesiol Section Body Doc Link 17583593 Disease Relevance 0 Pain Relevance 0

Although they are historically characterized as transcriptional activators, several reports have recently defined AP-1 and NF-?

Negative_regulation (defined) of AP-1

18) Confidence 0.23 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906809 Disease Relevance 0.12 Pain Relevance 0.06

Downregulation of transcription factors such as JUN has been observed in advanced stages of other cancers and its loss of activity has been postulated to be involved in this transition [40].

Negative_regulation (Downregulation) of JUN associated with cancer

19) Confidence 0.22 Published 2007 Journal BMC Cancer Section Body Doc Link PMC1865555 Disease Relevance 1.16 Pain Relevance 0.04

After 1 h exposure to L. plantarum WCFS1, four major transcriptional regulators were all found to be downregulated: the oncogene product MYC (c-Myc), FOS (c-Fos), JUN (c-Jun) and the p65 subunit of the NF-?

Negative_regulation (downregulated) of c-Jun

20) Confidence 0.18 Published 2008 Journal BMC Genomics Section Body Doc Link PMC2519092 Disease Relevance 0.72 Pain Relevance 0

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