Eosinophils Contribute to Intestinal Inflammation via Chemoattractant Receptor-homologous Molecule Expressed on Th2 Cells, CRTH2, in Experimental Crohn’s Disease

Radnai, B; Sturm, Eva; Stančić, Angela; Jandl, Katharina; Labocha, Sandra; Ferreiròs, Nerea; Grill, Magdalena; Hasenoehrl, Carina; Gorkiewicz, Gregor; Marsche, Gunther; Heinemann, Ákos; Högenauer, Christoph; Schicho, Rudolf

doi:10.1093/ecco-jcc/jjw061

Cited by 26 publications

(25 citation statements)

References 44 publications

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“…These studies point to a beneficial effect of DP1 in colitis that PGD 2 -G could be part of. Moreover, because DP2 activation was shown to be deleterious in colitis (8,21), the fact that the affinity of PGD 2 -G for DP1 is 10-fold higher than its affinity for DP2 might explain why PGD 2 -G exerts beneficial effects not reproduced by PGD 2 , which has the same affinity for both receptors. Indeed, although anti-inflammatory effects of PGD 2 have been reported in other models (4,5), the effect of PGD 2 itself was not studied in colitis, although some reports would suggest potential beneficial effects.…”

Section: Discussionmentioning

confidence: 99%

“…PGD 2 (1 mg/kg), PGD 2 -EA (1 mg/kg), the DP1 antagonist MK0524 (1 mg/kg), and the peroxisome proliferatoractivated receptor (PPAR)g antagonist GW9662 (1 mg/kg) were administered using the same administration scheme and vehicle as PGD 2 -G I. The dose regimen of PGD 2 and PGD 2 -EA was based on that of PGD 2 -G. Doses of MK0524 and GW9662 were based on previous reports (8,(21)(22)(23).…”

Section: Dss-induced Acute Murine Colitis Modelmentioning

confidence: 99%

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The endogenous bioactive lipid prostaglandin D ₂ ‐glycerol ester reduces murine colitis via DP1 and PPARγ receptors

et al. 2018

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Cyclooxygenase-2 (COX-2) has long been implicated in the pathogenesis of inflammatory bowel diseases (IBDs). COX-2 is mostly known for the production of prostaglandins (PGs) from arachidonic acid. However, it also metabolizes the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide into the less well-studied bioactive lipids PG-glycerol esters (PG-Gs) and PG-ethanolamides (PG-EAs or prostamides). We previously showed that PGD-G, a product of 2-AG oxygenation by COX-2, has anti-inflammatory effects. Therefore, we used the dextran sulfate sodium (DSS)-induced model of colitis in mice to explore the role of PGD-G in murine models of IBD. Colon inflammation was assessed using macroscopic and histologic scores, myeloperoxidase activity, and expression of inflammatory mediators by real-time quantitative PCR and ELISA. We also compared the effects of PGD-G with those of PGD and PGD-EA. Finally, we used receptor antagonists to gain mechanistic insight into the receptors responsible for the observed effects. PGD-G reduced DSS-induced colitis, but PGD and PGD-EA did not have the same effect. Furthermore, we showed that PGD-G is an agonist of the PGD receptor 1 (DP1) and that some of the effects of PGD-G were blocked by antagonism of peroxisome proliferator-activated receptor γ and DP1. Therefore, PGD-G could be one of the products from the COX-2/prostaglandin D synthase axis to exert beneficial effects in colitis.-Alhouayek, M., Buisseret, B., Paquot, A., Guillemot-Legris, O., Muccioli, G. G. The endogenous bioactive lipid prostaglandin D-glycerol ester reduces murine colitis via DP1 and PPARγ receptors.

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Section: Discussionmentioning

confidence: 99%

Section: Dss-induced Acute Murine Colitis Modelmentioning

confidence: 99%

The endogenous bioactive lipid prostaglandin D ₂ ‐glycerol ester reduces murine colitis via DP1 and PPARγ receptors

et al. 2018

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“…AA is converted into PGs by COX activity, which generate PGD 2 and PGE 2 as the representative lipid mediators. The PGD 2 -chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) pathway induces dextran sodium sulfate (DSS)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis (22, 23). Eosinophil infiltration into colon is inhibited by CRTH2 antagonist treatment in TNBS-induced colitis (23).…”

Section: ω6 Fatty Acid Metabolites Have Opposing Roles In Pro-and Antmentioning

confidence: 99%

Host- and Microbe-Dependent Dietary Lipid Metabolism in the Control of Allergy, Inflammation, and Immunity

2019

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The intestine is the largest immune organ in the body, provides the first line of defense against pathogens, and prevents excessive immune reactions to harmless or beneficial non-self-materials, such as food and intestinal bacteria. Allergic and inflammatory diseases in the intestine occur as a result of dysregulation of immunological homeostasis mediated by intestinal immunity. Several lines of evidence suggest that gut environmental factors, including nutrition and intestinal bacteria, play important roles in controlling host immune responses and maintaining homeostasis. Among nutritional factors, ω3 and ω6 essential polyunsaturated fatty acids (PUFAs) profoundly influence the host immune system. Recent advances in lipidomics technology have led to the identification of lipid mediators derived from ω3- and ω6-PUFAs. In particular, lipid metabolites from ω3-PUFAs (e.g., eicosapentaenoic acid and docosahexaenoic acid) have recently been shown to exert anti-allergic and anti-inflammatory responses; these metabolites include resolvins, protectins, and maresins. Furthermore, a new class of anti-allergic and anti-inflammatory lipid metabolites of 17,18-epoxyeicosatetraenoic acid has recently been identified in the control of allergic and inflammatory diseases in the gut and skin. Although these lipid metabolites were found to be endogenously generated in the host, accumulating evidence indicates that intestinal bacteria also participate in lipid metabolism and thus generate bioactive unique lipid mediators. In this review, we discuss the production machinery of lipid metabolites in the host and intestinal bacteria and the roles of these metabolites in the regulation of host immunity.

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“…CRTH2 associated with Th2 responses would be an attractive target in melanoma as this chemokine expression is increased in patients with a multi-metastatic disease (Table 3 ). CRTH2 is also expressed on eosinophils, basophils, and some monocytes/macrophages ( 155 ), immune subsets which all convey a distinct prognosis in melanoma ( 84 , 156 ). Initially designed for targeting CRTH2 + T cells involved in respiratory diseases ( 157 , 158 ), CRTH2 antagonists could be indicated in multi-metastatic melanoma patients with high CRTH2 expression.…”

Section: Potential For Targetingmentioning

confidence: 99%

Targeting Chemokines and Chemokine Receptors in Melanoma and Other Cancers

et al. 2018

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The tumor microenvironment is highly heterogeneous. It is composed of a diverse array of immune cells that are recruited continuously into lesions. They are guided into the tumor through interactions between chemokines and their receptors. A variety of chemokine receptors are expressed on the surface of both tumor and immune cells rendering them sensitive to multiple stimuli that can subsequently influence their migration and function. These features significantly impact tumor fate and are critical in melanoma control and progression. Indeed, particular chemokine receptors expressed on tumor and immune cells are strongly associated with patient prognosis. Thus, potential targeting of chemokine receptors is highly attractive as a means to quench or eliminate unconstrained tumor cell growth.

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Eosinophils Contribute to Intestinal Inflammation via Chemoattractant Receptor-homologous Molecule Expressed on Th2 Cells, CRTH2, in Experimental Crohn’s Disease

Abstract: CRTH2 plays a pro-inflammatory role in TNBS-induced colitis. Eosinophils contribute to the severity of the inflammation, which is improved by a selective CRTH2 antagonist. CRTH2 may, therefore, represent an important target in the pharmacotherapy of CD.

Cited by 26 publications

References 44 publications

The endogenous bioactive lipid prostaglandin D ₂ ‐glycerol ester reduces murine colitis via DP1 and PPARγ receptors

The endogenous bioactive lipid prostaglandin D ₂ ‐glycerol ester reduces murine colitis via DP1 and PPARγ receptors

Host- and Microbe-Dependent Dietary Lipid Metabolism in the Control of Allergy, Inflammation, and Immunity

Targeting Chemokines and Chemokine Receptors in Melanoma and Other Cancers

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Eosinophils Contribute to Intestinal Inflammation via Chemoattractant Receptor-homologous Molecule Expressed on Th2 Cells, CRTH2, in Experimental Crohn’s Disease

Abstract: CRTH2 plays a pro-inflammatory role in TNBS-induced colitis. Eosinophils contribute to the severity of the inflammation, which is improved by a selective CRTH2 antagonist. CRTH2 may, therefore, represent an important target in the pharmacotherapy of CD.

Cited by 26 publications

References 44 publications

The endogenous bioactive lipid prostaglandin D 2 ‐glycerol ester reduces murine colitis via DP1 and PPARγ receptors

The endogenous bioactive lipid prostaglandin D 2 ‐glycerol ester reduces murine colitis via DP1 and PPARγ receptors

Host- and Microbe-Dependent Dietary Lipid Metabolism in the Control of Allergy, Inflammation, and Immunity

Targeting Chemokines and Chemokine Receptors in Melanoma and Other Cancers

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Product

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The endogenous bioactive lipid prostaglandin D ₂ ‐glycerol ester reduces murine colitis via DP1 and PPARγ receptors

The endogenous bioactive lipid prostaglandin D ₂ ‐glycerol ester reduces murine colitis via DP1 and PPARγ receptors