INT4804

Context Info Confidence 0.68 First Reported 1992 Last Reported 2008 Negated 3 Speculated 0 Reported most in Body Documents 10 Total Number 49 Disease Relevance 21.43 Pain Relevance 11.14

isomerase activity (PTGDS) transport (PTGDS) extracellular space (PTGDS) extracellular region (PTGDS) Golgi apparatus (PTGDS) nucleus (PTGDS)

Anatomy Link Frequency cartilage 12 chondrocytes 8 skin 6 Notch 4 mast cells 4 PTGDS (Homo sapiens)

Pain Link Frequency Relevance Heat Morphine 16 99.88 Buprenorphine 16 99.88 Osteoarthritis 1880 99.84 Inflammation 890 99.24 Multiple sclerosis 40 97.48 headache 54 96.28 Migraine 37 95.88 cytokine 210 95.16 metalloproteinase 162 93.72 ketamine 4 92.00

Disease Link Frequency Relevance Heat Increased Venous Pressure Under Development 15 99.92 Osteoarthritis 1920 99.84 Body Weight 1 99.60 Disease 322 99.48 INFLAMMATION 979 99.24 Atherosclerosis 120 98.48 Hypertension 42 97.80 Injury 40 97.80 Pleurisy 40 97.52 Demyelinating Disease 40 97.48

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Morphine did not induce de novo synthesis of PGD2 from skin mast cells.

Neg (not) Positive_regulation (induce) of Gene_expression (synthesis) of PGD2 in skin associated with morphine

1) Confidence 0.68 Published 1992 Journal Anesthesiology Section Abstract Doc Link 1280014 Disease Relevance 0 Pain Relevance 1.00

Enhanced production of PGD2 was also described during the resolution phase of the wound-healing process [47].

Positive_regulation (Enhanced) of Gene_expression (production) of PGD2 associated with injury

2) Confidence 0.67 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.90 Pain Relevance 0.23

Indeed, the production of PGD2 is markedly elevated during the resolution of inflammation in carrageenan-induced pleurisy in rats, and exogenous PGD2 significantly reduces neutrophil levels in the inflammatory exudates [10,11].

Positive_regulation (elevated) of Gene_expression (production) of PGD2 in neutrophil associated with inflammation and pleurisy

3) Confidence 0.67 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.97 Pain Relevance 0.25

led to a time- and concentration-dependent upregulation of L-PGDS expression and PGD2 production.

Positive_regulation (upregulation) of Gene_expression (production) of PGD2

4) Confidence 0.67 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 1.04 Pain Relevance 0.31

This is supported by the observation that increased biosynthesis of PGD2 is associated with reduced production of PGE2 in several in vitro studies [49,50].

Positive_regulation (increased) of Gene_expression (biosynthesis) of PGD2

5) Confidence 0.67 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 1.17 Pain Relevance 0.27

Morphine only induced histamine and tryptase release from HSMC, but not the de novo synthesis of PGD2.

Neg (not) Positive_regulation (induced) of Gene_expression (synthesis) of PGD2 in HSMC associated with morphine

6) Confidence 0.65 Published 1993 Journal Ann Fr Anesth Reanim Section Abstract Doc Link 7690200 Disease Relevance 0 Pain Relevance 0.51

upregulates L-PGDS expression, we evaluated the roles played by downstream signalling cascades using specific pharmacological inhibitors.

Positive_regulation (upregulates) of Gene_expression (expression) of L-PGDS

7) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.37 Pain Relevance 0.18

As shown in Figures 4e and 4f, the increased expression of L-PGDS protein was accompanied by a time- and dose-dependent increase in PGD2 production.

Positive_regulation (increased) of Gene_expression (expression) of L-PGDS

8) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.05 Pain Relevance 0.03

Increased expression of L-PGDS was described in other diseases such as atherosclerosis [22], multiple sclerosis [38], diabetes [39] essential hypertension [40], and Tay-Sachs and Sandhoff diseases [41].

Positive_regulation (Increased) of Gene_expression (expression) of L-PGDS associated with multiple sclerosis, diabetes mellitus, atherosclerosis, hypertension and disease

9) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 1.07 Pain Relevance 0.32

Together, these data indicate that the expression level of L-PGDS is increased in OA cartilage.

Positive_regulation (increased) of Gene_expression (expression) of L-PGDS in cartilage associated with osteoarthritis

10) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.69 Pain Relevance 0.34

led to a time- and concentration-dependent upregulation of L-PGDS expression and PGD2 production.

Positive_regulation (upregulation) of Gene_expression (expression) of L-PGDS

11) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 1.04 Pain Relevance 0.31

As shown in Figures 4e and 4f, the increased expression of L-PGDS protein was accompanied by a time- and dose-dependent increase in PGD2 production.

Positive_regulation (increase) of Gene_expression (production) of PGD2

12) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0 Pain Relevance 0

-induced increase in L-PGDS expression corresponded with an increase in PGDS activity, we measured PGD2 levels in conditioned media.

Positive_regulation (increase) of Gene_expression (expression) of L-PGDS

13) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.11 Pain Relevance 0.06

The upregulation of L-PGDS mRNA expression in chondrocytes requires de novo protein synthesis

Positive_regulation (upregulation) of Gene_expression (expression) of L-PGDS mRNA in chondrocytes

14) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0 Pain Relevance 0

-induced upregulation of L-PGDS expression.

Positive_regulation (upregulation) of Gene_expression (expression) of L-PGDS

15) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0 Pain Relevance 0

-induced L-PGDS expression in human chondrocytes, we assessed the effect of DAPT.

Positive_regulation (induced) of Gene_expression (expression) of L-PGDS in chondrocytes

16) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.09 Pain Relevance 0

-induced L-PGDS expression in chondrocytes because DAPT, a Notch signalling inhibitor, blocked this process.

Positive_regulation (induced) of Gene_expression (expression) of L-PGDS in Notch

17) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.05 Pain Relevance 0.03

The enhanced expression of L-PGDS in the superficial and middle zones of cartilage could potentially be due to the increased level of the proinflammatory cytokine IL-1?

Positive_regulation (enhanced) of Gene_expression (expression) of L-PGDS in cartilage associated with cytokine

18) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 1.02 Pain Relevance 0.32

Therefore, one could speculate that upregulation of L-PGDS expression by IL-1?

Positive_regulation (upregulation) of Gene_expression (expression) of L-PGDS

19) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0 Pain Relevance 0

-induced upregulation of L-PGDS protein expression.

Positive_regulation (upregulation) of Gene_expression (expression) of L-PGDS

20) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.26 Pain Relevance 0.13

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