Expression of prostaglandin D synthase and the prostaglandin D2 receptors DP and CRTH2 in human nasal mucosa

Nantel, F.; Fong, Carolyn M.; Lamontagne, Sonia; Wright, D. Hamish; Giaid, Adel; Desrosiers, Martin; Metters, Kathleen M.; O’Neill, Gary P.; Gervais, François G.

doi:10.1016/j.prostaglandins.2003.12.002

Cited by 71 publications

(35 citation statements)

References 18 publications

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“…One of the PGD 2 receptors, DP1, was expressed in nasal mucosa in epithelial goblet cells, serous glands, vascular endothelium, epithelium, and in some of the infiltrating inflammatory cells including eosinophils (45). We found that H-PGDS and DP1 were highly expressed in human primary nasal epithelial cells.…”

Section: Discussionmentioning

confidence: 69%

The Extracellular Signal-regulated Kinase Mitogen-activated Protein Kinase/Ribosomal S6 Protein Kinase 1 Cascade Phosphorylates cAMP Response Element-binding Protein to Induce MUC5B Gene Expression via d-Prostanoid Receptor Signaling

Choi

Lee

Aoyagi

et al. 2011

Journal of Biological Chemistry

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Mucus hypersecretion is a prominent feature of respiratory diseases, and MUC5B is a major airway mucin. Mucin gene expression can be affected by inflammatory mediators, including prostaglandin (PG) D 2, an inflammatory mediator synthesized by hematopoietic PGD synthase (H-PGDS). PGD 2 binds to either D-prostanoid receptor (DP1) or chemoattractant receptor homologous molecule expressed on T-helper type 2 cells (CRTH2). We investigated the mechanisms by which PGD 2 induces MUC5B gene expression in airway epithelial cells. Western blot analysis showed that H-PGDS was highly expressed in nasal polyps. Similar results were obtained for PGD 2 expression. In addition, we could clearly detect the expressions of both H-PGDS and DP1 in nasal epithelial cells but not CRTH2. We demonstrated that PGD 2 increased MUC5B gene expression in normal human nasal epithelial cells as well as in NCI-H292 cells in vitro. S5751, a DP1 antagonist, inhibited PGD 2 -induced MUC5B expression, whereas a CRTH2 antagonist (OC0459) did not. These data suggest that PGD 2 induced MUC5B expression via DP1. Pretreatment with extracellular signal-regulated kinase (ERK) inhibitor (PD98059) blocked both PGD 2 -induced ERK mitogen-activated protein kinase (MAPK) activation and MUC5B expression. Proximity ligation assays showed direct interaction between RSK1 and cAMP response element-binding protein (CREB). Stimulation with PGD 2 caused an increase in intracellular cAMP levels, whereas intracellular Ca 2؉ did not have such an effect. PGD 2 -induced MUC5B mRNA levels were regulated by CREB via direct interaction with two cAMP-response element sites (؊921/؊914 and ؊900/؊893). Finally, we demonstrated that PGD 2 can induce MUC5B overproduction via ERK MAPK/ RSK1/CREB signaling and that DP1 receptor may have suppressive effects in controlling MUC5B overproduction in the airway.Mucus secretion in the airway, including the nasal and paranasal sinus cavities, is drained by the mucociliary transport system (1). Normal mucus secretion is essential for survival (2), but upregulation of mucin gene expression is a major manifestation of chronic airway diseases such as allergic rhinitis, asthma, and cystic fibrosis (3, 4). Patients suffering from these diseases have pathological abnormalities in both the submucosal glands and surface epithelium, characterized by inflammation, increased mucus cell number, and increased airway mucus. Several classes of inflammatory mediators have been implicated in the process of mucus hypersecretion based on their ability to stimulate secretion from cultured cells and tissue explants (5). These inflammatory mediators are lipopolysaccharides (6), reactive oxygen species (7), and arachidonic acid metabolites (8, 9).A total of 20 different mucin genes have been identified and subdivided into two groups, membrane-bound and secreted mucins, according to Human Genome Mapping conventions. The secreted mucins are MUC5AC, MUC5B, MUC6, and MUC19 (10 -13). Mucins are primarily synthesized by two different cell types in the airway tract, namely...

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Section: Discussionmentioning

confidence: 69%

The Extracellular Signal-regulated Kinase Mitogen-activated Protein Kinase/Ribosomal S6 Protein Kinase 1 Cascade Phosphorylates cAMP Response Element-binding Protein to Induce MUC5B Gene Expression via d-Prostanoid Receptor Signaling

Choi

Lee

Aoyagi

et al. 2011

Journal of Biological Chemistry

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“…The lack of in vitro eosinophil chemotactic activity of BW245C (Monneret et al, 2001) suggests that activation of the DP 1 receptor affects lung eosinophil numbers by an indirect mechanism, possibly due to the release of macrophage-derived chemokine (MDC/CCL22) (Honda et al, 2003). Activation of DP 1 receptors might also augment the responses to inflammatory mediators by increasing blood flow and vascular permeability in the affected tissue (Flower et al, 1976), consistent with the expression of these receptors on endothelial cells (Nantel et al, 2004). Alternatively, stimulation of DP 1 receptors on eosinophils could increase their survival in the lung, as shown for BW245C (although not for PGD 2 itself) in vitro (Gervais et al, 2001).…”

Section: Discussionmentioning

confidence: 87%

“…Furthermore, PGD 2 was shown to increase the expression of MDC by airway epithelial cells (Honda et al, 2003). The identity of the receptor responsible for these effects is not known, although the DP 1 receptor would seem to be the most likely candidate, because it is expressed on airway epithelial cells, in contrast to the DP 2 receptor, which is not (Hirai et al, 2001;Nantel et al, 2004). There are several possible explanations for the differences between the two studies.…”

Section: Induction Of Pulmonary Eosinophilia By Pgd 2 and Dp 2 Agonismentioning

confidence: 92%

Effects of Prostaglandin D2, 15-Deoxy-Δ12,14-prostaglandin J2, and Selective DP1 and DP2 Receptor Agonists on Pulmonary Infiltration of Eosinophils in Brown Norway Rats

Almishri¹,

Cossette²,

Rokach³

et al. 2005

The Journal of Pharmacology and Experimental Therapeutics

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Prostaglandin (PG) D 2 is an arachidonic acid metabolite that is released by allergen-stimulated mast cells. It is a potent in vitro chemoattractant for human eosinophils, acting through the DP 2 receptor/chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Furthermore, there is in vivo evidence that PGD 2 contributes to allergen-induced pulmonary eosinophilia via its classic DP 1 receptor. The PGD 2 -derived product 15-deoxy-⌬ 12,14 -PGJ 2 is widely used as a peroxisome proliferator-activated receptor ␥ agonist and has been shown to have anti-inflammatory properties. However, this substance can also activate eosinophils in vitro through the DP 2 receptor. The objectives of the present study were to determine whether PGD 2 and 15-deoxy-⌬ 12,14 -PGJ 2 can induce pulmonary eosinophilia, and, if so, to examine the abilities of selective DP 1 and DP 2 receptor agonists to induce this response. Brown Norway rats were treated by intratracheal instillation of PGs. Vehicle and 5-oxo-6,8,11,14-eicosatetraenoic acid were used as negative and positive controls, respectively. Lung eosinophils were identified by immunostaining of lung sections with an antibody to major basic protein. Both PGD 2 and 15-deoxy-⌬ 12,14 -PGJ 2 induced robust eosinophilic responses that were apparent by 12 h and persisted for at least 48 h. Two selective DP 2 receptor agonists, 15R-methyl-PGD 2 and 13-14-dihydro-15-keto-PGD 2 , induced similar responses, the former being more potent than PGD 2 , whereas the latter was less potent. The selective DP 1 receptor agonist BW245C [(4S)-(3-[(3R,S)-3-cyclohexyl-3-hydroxypropyl]-2,5-dioxo)-4-imidazolidineheptanoic acid] was completely inactive. We conclude that PGD 2 and 15-deoxy-⌬ 12,14 -PGJ 2 induce eosinophil infiltration into the lungs through the DP 2 receptor. The potent in vitro DP 2 receptor agonist 15R-methyl-PGD 2 is also very active in vivo and should be a useful tool in examining the role of this receptor.Prostaglandin (PG) D 2 is a metabolite of arachidonic acid that is formed by the action of PGD synthase on the cyclooxygenase product PGH 2 . There are two enzymes that catalyze this reaction: lipocalin-type PGD synthase, which is found in the central nervous system and hematopoietic PGD synthase, which is present in antigen-presenting cells, mast cells (Urade and Hayaishi, 2000), and Th2 cells . The association of PGD 2 with mast cells has focused attention on its possible role in asthma and other allergic diseases. High levels of this prostaglandin are rapidly released into the airways after allergen challenge of asthmatic human subjects (Murray et al., 1986).The recent finding by Narumiya's group that disruption of the classic G s -coupled (DP 1 ) receptor for PGD 2 protects mice against asthma-like responses after antigen challenge (Matsuoka et al., 2000) has provoked considerable interest in the role of PGD 2 in this disease. Mice lacking this receptor exhibit reduced pulmonary eosinophilia, hyperresponsiveness, and Th2 cytokine levels in response to antigen...

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“…In addition to defining a more severe subgroup, PGD 2 likely contributes to the severity of AERD through its myriad of biological activities that include inducing vasodilation and vascular leakage as well as bronchoconstriction. Many stromal and inflammatory cells found in AERD tissue express receptors for PGD 2 , including eosinophils, basophils, mast cells, epithelium, endothelium, and dendritic cells [32][33][34][35] . In addition to producing PGD 2 , eosinophils chemotax in response to PGD 2 which thereby worsen tissue eosinophilia 32,34 .…”

Section: Discussionmentioning

confidence: 99%

Eosinophil Production of PGD2 in Aspirin-Exacerbated Respiratory Disease

Steinke

Negri

Baker

et al. 2016

Journal of Allergy and Clinical Immunology

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Background-Aspirin-exacerbated respiratory disease (AERD) differs from aspirin tolerant disease due in part to eosinophilic tissue infiltration and over-expression of arachidonic acid metabolic pathway components that lead to enhanced secretion of cysteinyl leukotrienes (CysLT) and prostaglandin D 2 (PGD 2 ) observed constitutively and, paradoxically, in response to aspirin and other cyclooxygenase inhibitors. We have previously demonstrated the capacity of interferon (IFN)-γ to drive CysLT expression and response.

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Expression of prostaglandin D synthase and the prostaglandin D2 receptors DP and CRTH2 in human nasal mucosa

Cited by 71 publications

References 18 publications

The Extracellular Signal-regulated Kinase Mitogen-activated Protein Kinase/Ribosomal S6 Protein Kinase 1 Cascade Phosphorylates cAMP Response Element-binding Protein to Induce MUC5B Gene Expression via d-Prostanoid Receptor Signaling

The Extracellular Signal-regulated Kinase Mitogen-activated Protein Kinase/Ribosomal S6 Protein Kinase 1 Cascade Phosphorylates cAMP Response Element-binding Protein to Induce MUC5B Gene Expression via d-Prostanoid Receptor Signaling

Effects of Prostaglandin D2, 15-Deoxy-Δ12,14-prostaglandin J2, and Selective DP1 and DP2 Receptor Agonists on Pulmonary Infiltration of Eosinophils in Brown Norway Rats

Eosinophil Production of PGD2 in Aspirin-Exacerbated Respiratory Disease

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