INT86534

Context Info Confidence 0.62 First Reported 2000 Last Reported 2011 Negated 0 Speculated 3 Reported most in Body Documents 81 Total Number 104 Disease Relevance 57.81 Pain Relevance 23.62

cytosol (MAPK14) nucleoplasm (MAPK14) signal transduction (MAPK14) nucleus (MAPK14) response to stress (MAPK14) cytoplasm (MAPK14)

Anatomy Link Frequency chondrocytes 9 annulus 3 fibroblasts 2 neurons 2 finger 1 MAPK14 (Homo sapiens)

Pain Link Frequency Relevance Heat Inflammation 1141 100.00 cytokine 1190 99.98 Eae 10 99.72 metalloproteinase 181 99.66 Osteoarthritis 2749 99.40 Kinase C 32 99.20 Nicotine 192 99.12 Central nervous system 257 99.04 aspirin 22 98.98 IPN 8 98.78

Disease Link Frequency Relevance Heat INFLAMMATION 1208 100.00 Apoptosis 914 100.00 Stress 462 100.00 Death 200 99.92 Alzheimer's Dementia 36 99.76 Neurodegenerative Disease 48 99.60 Breast Cancer 112 99.52 Cold Sores 367 99.48 Osteoarthritis 2733 99.40 Aging 263 99.36

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Sodium salicylate-induced apoptosis of human peripheral blood eosinophils is independent of the activation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase.

Positive_regulation (activation) of p38 in eosinophils associated with apoptosis

1) Confidence 0.62 Published 2000 Journal Int. Arch. Allergy Immunol. Section Title Doc Link 10686508 Disease Relevance 0.66 Pain Relevance 0.08

Secretion requires intracellular calcium mobilization and activation of phosphinositol-3 kinase and p38 mitogen activated kinase.

Positive_regulation (activation) of p38

2) Confidence 0.60 Published 2007 Journal Curr Rheumatol Rep Section Abstract Doc Link 18177605 Disease Relevance 0.48 Pain Relevance 1.18

The activation of inflammation-associated enzymes such as p38 mitogen-activated protein kinase (p38 MAPK) and cycloxygenase-2 (COX-2) is not restricted to glial cells but also found in neurons and may contribute to intraneuronal damage.

Positive_regulation (activation) of p38 mitogen-activated protein kinase in neurons associated with inflammation

3) Confidence 0.59 Published 2002 Journal Curr. Med. Chem. Section Abstract Doc Link 11860350 Disease Relevance 1.35 Pain Relevance 0.66

activates p38?

Positive_regulation (activates) of p38

4) Confidence 0.58 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 1.02 Pain Relevance 0.45

-induced activation of p38-MAPK in human OA chondrocytes.

Positive_regulation (activation) of p38 in chondrocytes associated with osteoarthritis

5) Confidence 0.58 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.55 Pain Relevance 0.28

-induced activation of p38-MAPK isoforms in human OA chondrocytes.

Positive_regulation (activation) of p38 in chondrocytes associated with osteoarthritis

6) Confidence 0.58 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.66 Pain Relevance 0.33

-induced activation of p38?

Positive_regulation (activation) of p38

7) Confidence 0.58 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.61 Pain Relevance 0.31

was more pronounced on the phosphorylation of MKK3 as compared to MKK6 suggesting that MKK3 may be the primary kinase involved in the activation of p38-MAPK in human OA chondrocytes.

Positive_regulation (activation) of p38 in chondrocytes associated with osteoarthritis

8) Confidence 0.58 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.60 Pain Relevance 0.30

-induced activation of p38-MAPK in human OA chondrocytes

Positive_regulation (activation) of p38 in chondrocytes associated with osteoarthritis

9) Confidence 0.58 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 1.04 Pain Relevance 0.43

-induced activation of p38?

Positive_regulation (activation) of p38

10) Confidence 0.58 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 1.06 Pain Relevance 0.57

For instance, MKK6 is the major activator of p38-MAPK in cells exposed to osmotic stress [13] and MKK3 is required for full activation of p38-MAPK in murine embryonic fibroblasts [38].

Positive_regulation (activation) of p38 in fibroblasts associated with stress

11) Confidence 0.58 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.66 Pain Relevance 0.33

Our results demonstrate a novel mechanism of sulindac-induced apoptosis in human MM cells, namely, accumulation of p53, Bax, and Bak in mitochondria mediated by p38 MAPK activation downstream of ROS production.

Positive_regulation (activation) of p38 associated with multiple myeloma and apoptosis

12) Confidence 0.47 Published 2007 Journal Apoptosis Section Abstract Doc Link 17136320 Disease Relevance 1.12 Pain Relevance 0

It could also activate c-Jun N-terminal kinase (JNK) and p38 MAPK but not extracellular signal-regulated protein kinase (ERK) activity within 1 h.

Positive_regulation (activate) of p38

13) Confidence 0.45 Published 2000 Journal Int. Arch. Allergy Immunol. Section Body Doc Link 10686508 Disease Relevance 0.16 Pain Relevance 0

The activation of inflammation-associated enzymes such as p38 mitogen-activated protein kinase (p38 MAPK) and cycloxygenase-2 (COX-2) is not restricted to glial cells but also found in neurons and may contribute to intraneuronal damage.

Positive_regulation (activation) of p38 mitogen-activated protein kinase in neurons associated with inflammation

14) Confidence 0.42 Published 2002 Journal Curr. Med. Chem. Section Abstract Doc Link 11860350 Disease Relevance 1.35 Pain Relevance 0.66

-induced activation of p38-MAPK compared to the level noted in cells with knockdown expression of MKK6.

Positive_regulation (activation) of p38

15) Confidence 0.42 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.54 Pain Relevance 0.27

-induced activation of p38-MAPK (Figure 2b, c), but the inhibition of phosphorylation was more pronounced when the expression of MKK3 was knocked down compared to the knockdown of MKK6 (Figure 2b).

Positive_regulation (activation) of p38

16) Confidence 0.42 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.99 Pain Relevance 0.41

Key to these pathways are the evolutionarily conserved mitogen-activated protein kinases (MAPKs); of these, p38-MAPK (also known as MAPK14) has received considerable attention as potential therapeutic target for inflammatory and degenerative diseases such as OA [33]. p38-MAPK is thought to be crucial because selective p38-MAPK inhibitors block joint inflammation and destruction in several animal models of arthritis [12].

Positive_regulation (conserved) of p38 in joint associated with inflammation, disease, osteoarthritis and arthritis

17) Confidence 0.42 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 1.06 Pain Relevance 0.56

-induced production of MMPs by blocking the activation of p38-MAPK and the transcription factor NF-?

Positive_regulation (activation) of p38 associated with metalloproteinase

18) Confidence 0.42 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.92 Pain Relevance 0.55

Thus, treatment with PE affects particularly the activation of MKK3 which in turn has an impact on the activation of p38-MAPK downstream (summarized in Figure 6).

Positive_regulation (activation) of p38

19) Confidence 0.42 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.68 Pain Relevance 0.25

CONCLUSION: There is no direct relationship between the activation of JNK and p38 MAPK pathways and NaSal-induced apoptosis in human peripheral blood eosinophils.

Positive_regulation (activation) of p38 in blood

20) Confidence 0.41 Published 2000 Journal Int. Arch. Allergy Immunol. Section Body Doc Link 10686508 Disease Relevance 0.12 Pain Relevance 0

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