INT27758

Context Info Confidence 0.67 First Reported 1989 Last Reported 2009 Negated 0 Speculated 1 Reported most in Body Documents 20 Total Number 21 Disease Relevance 10.74 Pain Relevance 4.22

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

Anatomy Link Frequency cartilage 5 chondrocytes 2 neutrophils 2 macrophages 1 platelets 1 PTGDS (Homo sapiens)

Pain Link Frequency Relevance Heat agonist 28 100.00 Osteoarthritis 705 99.84 aspirin 4 99.70 Inflammation 337 99.68 cytokine 75 96.96 cINOD 17 96.28 fibrosis 4 93.20 Codeine 1 92.40 Multiple sclerosis 15 88.48 antagonist 5 78.28

Disease Link Frequency Relevance Heat Pleurisy 15 100.00 Osteoarthritis 720 99.84 INFLAMMATION 372 99.68 Urticaria 2 96.44 Arrhythmias 2 Under Development 15 95.88 Disease 126 93.56 Fibrosis 5 93.20 Hyperplasia 2 92.24 Atherosclerosis 51 90.48 Cough 91 90.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Indeed, increased levels of PGD2 are observed during the resolution phase of inflammation and the inflammation is exacerbated by COX inhibitors [10,11].

Positive_regulation (increased) of PGD2 associated with inflammation

1) Confidence 0.67 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 1.26 Pain Relevance 0.40

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

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

2) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.68 Pain Relevance 0.34

-induced L-PGDS upregulation, whereas an inhibitor of the ERK MAPK was without effect.

Positive_regulation (upregulation) of L-PGDS

3) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.28 Pain Relevance 0.14

Given the anti-inflammatory and anticatabolic roles of PGD2, it is reasonable to speculate that the upregulation of L-PGDS may act as a sort of chondroprotective mechanism.

Positive_regulation (upregulation) of L-PGDS associated with inflammation

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

-induced upregulation of L-PGDS.

Positive_regulation (upregulation) of L-PGDS

5) Confidence 0.59 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.06 Pain Relevance 0

to induce L-PGDS mRNA in chondrocytes contrasts with those required for other IL-1?

Positive_regulation (induce) of L-PGDS mRNA in chondrocytes

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

The findings of large increases in histamine accompanied by small increases in PGD2 in venous effluent of thermally challenged limbs of patients with cold- or heat-induced urticaria may suggest that their mast cells had been activated by a non-immunological stimulus.

Positive_regulation (increases) of PGD2 in limbs associated with urticaria

7) Confidence 0.58 Published 1989 Journal Clin. Exp. Allergy Section Abstract Doc Link 2667702 Disease Relevance 0.57 Pain Relevance 0.23

B in the upregulation of L-PGDS in leptomeningel cells [55], endothelial cells [56], and macrophages [57].

Positive_regulation (upregulation) of L-PGDS in macrophages

8) Confidence 0.42 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.17 Pain Relevance 0.08

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 (induced) of PGD2 in neutrophil associated with inflammation and pleurisy

9) Confidence 0.42 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 1.01 Pain Relevance 0.24

In whole-cell saturation-binding assays, 1 and 2 both increase the number of [(3)H]prostaglandin D2 (PGD2)-recognizing CRTH2 sites and the affinity of PGD2 for CRTH2.

Positive_regulation (increase) of prostaglandin D2

10) Confidence 0.41 Published 2005 Journal Mol. Pharmacol. Section Abstract Doc Link 15870392 Disease Relevance 0.15 Pain Relevance 0.15

upregulated L-PGDS mRNA and protein expressions as well as PGD2 production in a dose- and time-dependent manner.

Positive_regulation (upregulated) of L-PGDS mRNA

11) Confidence 0.39 Published 2008 Journal Arthritis Res Ther Section Abstract Doc Link PMC2656251 Disease Relevance 0.51 Pain Relevance 0.22

Given that the levels of L-PGDS are elevated in OA cartilage and that IL-1?

Positive_regulation (elevated) of L-PGDS in cartilage associated with osteoarthritis

12) Confidence 0.39 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.48 Pain Relevance 0.17

Our study has demonstrated for the first time that L-PGDS is upregulated in OA cartilage.

Positive_regulation (upregulated) of L-PGDS in cartilage associated with osteoarthritis

13) Confidence 0.39 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.63 Pain Relevance 0.29

L-PGDS and H-PGDS mRNAs were present in both healthy and OA cartilage, with higher levels of L-PGDS than H-PGDS (> 20-fold).

Positive_regulation (levels) of L-PGDS in cartilage associated with osteoarthritis

14) Confidence 0.39 Published 2008 Journal Arthritis Res Ther Section Abstract Doc Link PMC2656251 Disease Relevance 0.54 Pain Relevance 0.23

Once formed by COX-1 or COX-2, the unstable PGH2 intermediate is metabolized by specific PG synthase enzymes to generate the classical bioactive PGs, including PGE2, PGD2, PGF2?

Positive_regulation (generate) of PGD2

15) Confidence 0.39 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.42 Pain Relevance 0.22

Statistical evaluation for the cell score revealed a clear and significant increase in the number of chondrocytes staining positive for L-PGDS in OA cartilage (43% ± 6%, mean ± SEM) compared with healthy cartilage (20% ± 4%, mean ± SEM).

Spec (clear) Positive_regulation (increase) of L-PGDS in chondrocytes associated with osteoarthritis

16) Confidence 0.39 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656251 Disease Relevance 0.62 Pain Relevance 0.31

The levels of L-PGDS mRNA and protein were increased in OA compared with healthy cartilage.

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

17) Confidence 0.39 Published 2008 Journal Arthritis Res Ther Section Abstract Doc Link PMC2656251 Disease Relevance 0.54 Pain Relevance 0.23

Conversely, both Cicaprost and the PGD2 receptor agonist BW245C impaired RhoA activation, cofilin phosphorylation, F-actin polymerization and [Ca2+]i mobilization by TP?

Positive_regulation (activation) of PGD2 associated with agonist

18) Confidence 0.17 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0.05

Consistent with this, the specific PGD2 receptor (DP) agonist BW245C also significantly impaired RhoA activation (Fig. 7C) and cofilin phosphorylation in 1° h.AoSMCs.

Positive_regulation (activation) of PGD2 associated with agonist

19) Confidence 0.17 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0.10

Increased mast cells have been observed also in bronchoalveolar lavage fluid [25] and increased neutrophils in induced sputum [26], with increased concentration of histamine, PGD2 and PGE2, together with TNF?

Positive_regulation (increased) of PGD2 in neutrophils

20) Confidence 0.09 Published 2009 Journal Respir Res Section Body Doc Link PMC2688489 Disease Relevance 1.69 Pain Relevance 0.28

General Comments

This test has worked.