INT35486

Context Info Confidence 0.36 First Reported 1985 Last Reported 2010 Negated 4 Speculated 3 Reported most in Body Documents 39 Total Number 42 Disease Relevance 19.03 Pain Relevance 6.75

plasma membrane (PTGER2) signal transducer activity (PTGER2)

Anatomy Link Frequency plasma 8 fibroblasts 4 PGE2 2 blood 1 body 1 PTGER2 (Homo sapiens)

Pain Link Frequency Relevance Heat diclofenac 212 100.00 cINOD 203 100.00 COX-2 inhibitor 132 100.00 Inflammatory marker 43 100.00 Bioavailability 6 100.00 Inflammation 652 99.32 aspirin 45 99.06 Kinase C inhibitor 1 98.56 Potency 13 97.28 Inflammatory response 27 94.44

Disease Link Frequency Relevance Heat INFLAMMATION 810 100.00 Colon Cancer 222 100.00 Apoptosis 117 100.00 Ulcers 27 100.00 Herpes Simplex Virus 714 99.98 Cancer 440 99.76 Obesity 112 99.56 Hypertension 8 99.24 Colorectal Cancer 110 98.56 Endometriosis (extended) 72 98.24

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Therefore several mechanisms could account for indomethacin in regulating the bioavailability of PGE2.

Regulation (regulating) of PGE2 associated with bioavailability

1) Confidence 0.36 Published 2010 Journal BMC Gastroenterol Section Body Doc Link PMC2824707 Disease Relevance 0.72 Pain Relevance 0.09

Whether changes in levels of PGE2 are primary or secondary causes of CRN remains unclear.

Spec (Whether) Regulation (changes) of PGE2 in PGE2 associated with colorectal cancer

2) Confidence 0.26 Published 2010 Journal BMC Gastroenterol Section Body Doc Link PMC2824707 Disease Relevance 0.87 Pain Relevance 0.39

In normotensive and hypertensive humans, prostaglandins, particularly PGE2 and PGI2, affect blood pressure through control of vascular resistance, salt excretion, cardiac output, and renin secretion.

Regulation (affect) of PGE2 in blood associated with hypertension

3) Confidence 0.18 Published 1985 Journal Adv. Prostaglandin Thromboxane Leukot. Res. Section Abstract Doc Link 3159200 Disease Relevance 0.38 Pain Relevance 0.05

Intriguingly, changes in cAMP levels in response to particular PGE2 doses inversely correlate with their proliferative potency (compare Figs. 1A and 3A): Thus, mitogenic PGE2 doses either down regulate or do not ostensibly affect cAMP levels whereas anti or non-proliferative PGE2 concentrations do in all cases elevate cAMP.

Regulation (proliferative) of PGE2 associated with potency

4) Confidence 0.17 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2615781 Disease Relevance 0.23 Pain Relevance 0.05

Similarly, there is only a limited body of partially conflictive experimental data on the regulation of apoptosis in colorectal cancer cells by PGE2 [13,22-24].

Regulation (regulation) of PGE2 in body associated with colon cancer and apoptosis

5) Confidence 0.17 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2615781 Disease Relevance 0.57 Pain Relevance 0.03

More recently, a study comparing EP receptor expression in nasal biopsies from aspirin intolerant and tolerant patients showed an up-regulation of EP1 and EP2 in structural cells from aspirin intolerant subjects [15].

Regulation (regulation) of EP2 in structural cells associated with aspirin

6) Confidence 0.16 Published 2006 Journal Respir Res Section Body Doc Link PMC1481584 Disease Relevance 0.72 Pain Relevance 0.34

The objective of this study was to determine the effects of COX-2 inhibitors on amounts of PGE2 and IL-6 made by IL-1beta-stimulated gingival fibroblasts.

Regulation (effects) of PGE2 in fibroblasts associated with cox-2 inhibitor

7) Confidence 0.16 Published 2003 Journal J. Periodontol. Section Abstract Doc Link 14974816 Disease Relevance 0.43 Pain Relevance 0.27

Several enzymes and regulatory pathways control the level of PGE2 both in colonic cells and in the intercellular environment of colonic tissue, Figure 1.

Regulation (control) of PGE2

8) Confidence 0.16 Published 2010 Journal BMC Gastroenterol Section Body Doc Link PMC2824707 Disease Relevance 0.43 Pain Relevance 0.08

Finally, neither sodium nitroprusside nor zaprinast (both of which elevate cGMP levels) affected GM-CSF or PGE2 release.

Neg (nor) Regulation (affected) of PGE2 in PGE2

9) Confidence 0.15 Published 2005 Journal Eur. J. Pharmacol. Section Abstract Doc Link 15680249 Disease Relevance 0.10 Pain Relevance 0.88

The observed changes in PGE2, TNF alpha and annexin A2 corroborate anti-inflammatory effects of the diclofenac treatment in the overweight subjects.

Regulation (changes) of PGE2 associated with inflammation, diclofenac and overweight

10) Confidence 0.14 Published 2010 Journal BMC Med Genomics Section Body Doc Link PMC2837611 Disease Relevance 0.45 Pain Relevance 0.55

To confirm the lack of apoptosis regulation by PGE2, we monitored Annexin V-binding via FACS analysis (Fig. 2B).

Regulation (regulation) of PGE2 associated with apoptosis

11) Confidence 0.10 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2615781 Disease Relevance 1.03 Pain Relevance 0.12

While sialic acid levels were not different between groups, responses of PGE2 and CRP on diclofenac treatment differed significantly from responses on placebo treatment (PGE2: treatment × time interaction p = 0.017; hsCRP: treatment × time interaction p = 0.0273).

Regulation (responses) of PGE2 associated with diclofenac

12) Confidence 0.06 Published 2010 Journal BMC Med Genomics Section Body Doc Link PMC2837611 Disease Relevance 0.53 Pain Relevance 0.46

In addition to changes in PGE2, diclofenac intervention also altered levels of other plasma oxylipids, increasing 5,6-dihydroxy-eicosatrienoic acid (5,6-DHET) and 20-HETE (20-hydroxyeicosatetraenoic acid) and decreasing the linoleate derived 9,10-dihydroxyoctadecenoic acid (9,10-DHOME).

Regulation (changes) of PGE2 in plasma associated with diclofenac

13) Confidence 0.06 Published 2010 Journal BMC Med Genomics Section Body Doc Link PMC2837611 Disease Relevance 0.49 Pain Relevance 0.47

Firstly, effects of diclofenac on known inflammatory markers CRP, PGE2 and sialic acid were assessed.

Regulation (effects) of PGE2 associated with inflammatory marker and diclofenac

14) Confidence 0.06 Published 2010 Journal BMC Med Genomics Section Body Doc Link PMC2837611 Disease Relevance 0.57 Pain Relevance 0.45

In our previous study, we showed that KSHV modulates host factors COX-2/PGE2 for its own advantage to promote its latent (persistent) infection.

Regulation (modulates) of PGE2 associated with herpes simplex virus and infection

15) Confidence 0.05 Published 2010 Journal PLoS Pathogens Section Abstract Doc Link PMC2820536 Disease Relevance 2.32 Pain Relevance 0.25

Inhibition of PLA2 can effectively control both PGE2 and LTB4, but will also downregulate all the downstream AA metabolites including vasoactive eicosanoids, which has important physiological functions.

Regulation (control) of PGE2

16) Confidence 0.05 Published 2008 Journal Mol Syst Biol Section Body Doc Link PMC2673713 Disease Relevance 0.23 Pain Relevance 0.09

mol/l celecoxib (Figure 3 panels a [part iii] and c), suggesting that the celecoxib-mediated inhibition was dependent on PGE2.

Regulation (dependent) of PGE2

17) Confidence 0.05 Published 2006 Journal Breast Cancer Res Section Body Doc Link PMC1797025 Disease Relevance 0.16 Pain Relevance 0

Measurement of PGE2, IL-10 and IL-18 content in culture medium

Regulation (content) of PGE2

18) Confidence 0.04 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1794527 Disease Relevance 0 Pain Relevance 0

It therefore appears that, regardless of menopausal status, it is the circulating level of celecoxib that is important, with low levels having little influence on PGE2, and higher doses decreasing PGE2.

Neg (little) Regulation (influence) of PGE2 associated with endometriosis (extended)

19) Confidence 0.04 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2259321 Disease Relevance 0.27 Pain Relevance 0.04

M), while it had no effect on PGE2 production. 3.3.

Neg (no) Regulation (effect) of PGE2

20) Confidence 0.03 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2726438 Disease Relevance 0.17 Pain Relevance 0.14

General Comments

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