INT4809

Context Info Confidence 0.76 First Reported 1983 Last Reported 2011 Negated 1 Speculated 6 Reported most in Body Documents 103 Total Number 109 Disease Relevance 52.94 Pain Relevance 24.01

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

Anatomy Link Frequency cartilage 15 chondrocytes 8 skin 5 Notch 4 plaques 3 PTGDS (Homo sapiens)

Pain Link Frequency Relevance Heat Osteoarthritis 3305 100.00 Potency 4 100.00 cINOD 159 99.72 Buprenorphine 18 99.56 Inflammatory response 81 99.52 Morphine 24 99.52 cytokine 375 99.38 Inflammation 1678 99.28 aspirin 30 99.18 COX-2 inhibitor 119 98.14

Disease Link Frequency Relevance Heat Osteoarthritis 3336 100.00 Syndrome 49 100.00 Apoptosis 395 99.96 Atherosclerosis 222 99.84 Hypersensitivity 177 99.72 Increased Venous Pressure Under Development 23 99.66 INFLAMMATION 1856 99.60 Disease 744 99.48 Body Weight 3 99.44 Familial Adenomatous Polyposis 3 99.40

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Fentanyl (10(-5)-10(-3) M) did not induce histamine and tryptase release or the de novo synthesis of PGD2 or LTC4 from any mast cells.

Gene_expression (synthesis) of PGD2 in mast cells

1) Confidence 0.76 Published 1992 Journal Anesthesiology Section Abstract Doc Link 1280014 Disease Relevance 0 Pain Relevance 0.88

Buprenorphine also induced de novo synthesis of PGD2 and LTC4 from lung mast cells.

Gene_expression (synthesis) of PGD2 in mast cells associated with buprenorphine

2) Confidence 0.76 Published 1992 Journal Anesthesiology Section Abstract Doc Link 1280014 Disease Relevance 0 Pain Relevance 0.96

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

Gene_expression (synthesis) of PGD2 in skin associated with morphine

3) Confidence 0.76 Published 1992 Journal Anesthesiology Section Abstract Doc Link 1280014 Disease Relevance 0 Pain Relevance 1.00

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].

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

4) Confidence 0.75 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.96 Pain Relevance 0.25

This suggests that the balance between PGD2 and PGE2 contributes to the pathology of atherosclerosis and that a shift toward PGD2 synthesis may have an anti-inflammatory role.

Gene_expression (synthesis) of PGD2 associated with inflammation and atherosclerosis

5) Confidence 0.75 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 1.13 Pain Relevance 0.27

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].

Gene_expression (biosynthesis) of PGD2

6) Confidence 0.75 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 1.16 Pain Relevance 0.27

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

Gene_expression (production) of PGD2

7) Confidence 0.75 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 1.03 Pain Relevance 0.31

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

Gene_expression (production) of PGD2 associated with injury

8) Confidence 0.75 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.85 Pain Relevance 0.23

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

Gene_expression (synthesis) of PGD2 in HSMC associated with morphine

9) Confidence 0.73 Published 1993 Journal Ann Fr Anesth Reanim Section Abstract Doc Link 7690200 Disease Relevance 0 Pain Relevance 0.50

In contrast, buprenorphine caused histamine and tryptase release from HLMC, and not from HSMC, whilst it also induced de novo synthesis of PGD2 and LTC4 in HLMC.

Gene_expression (synthesis) of PGD2 in HLMC associated with buprenorphine

10) Confidence 0.73 Published 1993 Journal Ann Fr Anesth Reanim Section Abstract Doc Link 7690200 Disease Relevance 0 Pain Relevance 0.30

The muscle relaxants and hypnotics examined did not induce any de novo synthesis of PGD2 or LTC4 in mast cells.

Gene_expression (synthesis) of PGD2 in mast cells

11) Confidence 0.73 Published 1993 Journal Ann Fr Anesth Reanim Section Abstract Doc Link 7690200 Disease Relevance 0 Pain Relevance 0.50

upregulated, whereas PGD2 downregulated, the expression of L-PGDS in cultured chondrocytes.

Gene_expression (expression) of L-PGDS in chondrocytes

12) Confidence 0.66 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.51 Pain Relevance 0.22

-induced upregulation of L-PGDS expression.

Gene_expression (expression) of L-PGDS

13) Confidence 0.66 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0 Pain Relevance 0

Cipollone and colleagues [48] examined the expression of L-PGDS in atherosclerotic arteries and found lower expression of L-PGDS and higher expression of microsomal prostaglandin E synthase-1 (mPGES-1) in symptomatic plaques and found higher expression of L-PGDS and lower expression of mPGES-1 in asymptomatic ones.

Gene_expression (expression) of L-PGDS in plaques associated with atherosclerosis

14) Confidence 0.66 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.80 Pain Relevance 0.25

The biosynthesis of PGD2 from its precursor PGH2 is catalyzed by two PGD synthases (PGDSs): one is gluthatione-independent, the lipocaline-type PGDS (L-PGDS), and the other is glutathione-requiring, the hematopoietic PGDS (H-PGDS) [19].

Gene_expression (biosynthesis) of PGD2

15) Confidence 0.66 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.93 Pain Relevance 0.33

The production of PGD2 by chondrocytes is of particular interest since PGD2 is readily converted to 15d-PGJ2, a potent antiarthritic agent [14]. 15dPGJ2 downregulates the expression of a number of inflammatory and catabolic mediators involved in the pathogenesis of OA, including IL-1?

Gene_expression (production) of PGD2 in chondrocytes associated with inflammation and osteoarthritis

16) Confidence 0.66 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 1.18 Pain Relevance 0.35

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.

Gene_expression (production) of PGD2

17) Confidence 0.66 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0 Pain Relevance 0

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

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

18) Confidence 0.66 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.68 Pain Relevance 0.34

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

Gene_expression (expression) of L-PGDS

19) Confidence 0.66 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.37 Pain Relevance 0.18

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

Gene_expression (expression) of L-PGDS mRNA in chondrocytes

20) Confidence 0.66 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0 Pain Relevance 0

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