The release of prostaglandin D2 from human skin in vivo and in vitro during immediate allergic reactions

Rm, Barr; Koro, Osamu; Francis, DM; Black, A. Kobza; Numata, Tsunemi; Mw, Greaves

doi:10.1111/j.1476-5381.1988.tb11588.x

Cited by 39 publications

(19 citation statements)

References 24 publications

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“…Such activity is presumed to significantly contribute to the mast cell-mediated localization of proinflammatory effectors at sites of inflammation [87]. Eosinophil and T H 2 infiltration into inflamed dermal tissues [112,115,116] and airways [85,117], including the lungs and nasal mucosa, is largely mediated through DP 2 receptors. DP 2 engagement has also been shown to enhance cytokine and cell adhesion molecule expression in a variety of cell types, including eosinophils and T H 2 lymphocytes [91,93,118].…”

Section: Pro-inflammatory Activitymentioning

confidence: 99%

Positioning prostanoids of the D and J series in the immunopathogenic scheme

Herlong

Scott

2006

Immunology Letters

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Section: Pro-inflammatory Activitymentioning

confidence: 99%

Positioning prostanoids of the D and J series in the immunopathogenic scheme

Herlong

Scott

2006

Immunology Letters

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“…3 is the predominant prostanoid species produced by allergen-activated mast cells (1,2) and has been implicated in the pathogenesis of allergic diseases such as allergic asthma and atopic dermatitis (1,3). Increased production or exposure to PGD 2 leads to elevated Th2-type cytokines and eosinophilic inflammation in murine asthma models (4,5).…”

Section: Prostaglandin D 2 (Pgd 2 )mentioning

confidence: 99%

Identification of Determinants of Ligand Binding Affinity and Selectivity in the Prostaglandin D2 Receptor CRTH2

Hata¹,

Lybrand

Breyer

2005

Journal of Biological Chemistry

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The chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) is a G protein-coupled receptor that mediates the pro-inflammatory effects of prostaglandin D 2 (PGD 2 ) generated in allergic inflammation. The CRTH2 receptor shares greatest sequence similarity with chemoattractant receptors compared with prostanoid receptors. To investigate the structural determinants of CRTH2 ligand binding, we performed site-directed mutagenesis of putative mCRTH2 ligand-binding residues, and we evaluated mutant receptor ligand binding and functional properties. Substitution of alanine at each of three residues in the transmembrane (TM) helical domains (His-106, TM III; Lys-209, TM V; and Glu-268, TM VI) and one in extracellular loop II (Arg-178) decreased PGD 2 binding affinity, suggesting that these residues play a role in binding PGD 2 . In contrast, the H106A and E268A mutants bound indomethacin, a nonsteroidal anti-inflammatory drug, with an affinity similar to the wild-type receptor. HEK293 cells expressing the H106A, K209A, and E268A mutants displayed reduced inhibition of intracellular cAMP and chemotaxis in response to PGD 2 , whereas the H106A and E268A mutants had functional responses to indomethacin similar to the wild-type receptor. Binding of PGE 2 by the E268A mutant was enhanced compared with the wild-type receptor, suggesting that Glu-268 plays a role in determining prostanoid ligand selectivity. Replacement of Tyr-261 with phenylalanine did not affect PGD 2 binding but decreased the binding affinity for indomethacin. These results provided the first details of the ligand binding pocket of an eicosanoid-binding chemoattractant receptor. Prostaglandin D 2 (PGD 2 )3 is the predominant prostanoid species produced by allergen-activated mast cells (1, 2) and has been implicated in the pathogenesis of allergic diseases such as allergic asthma and atopic dermatitis (1, 3). Increased production or exposure to PGD 2 leads to elevated Th2-type cytokines and eosinophilic inflammation in murine asthma models (4, 5). However, the molecular mechanism of PGD 2 action in the pathogenesis of allergic disease remains only partially characterized.PGD 2 exerts its effects through two G protein-coupled receptors (GPCRs), the D prostanoid receptor (DP) and the recently discovered chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). DP receptor signaling has been linked to NF-B activation (6) and may influence dendritic cell function leading to skewing of the T cell response toward a Th2 phenotype (7). Mice deficient in the DP receptor display reduced Th2-mediated airway inflammation in the ovalbumin-induced asthma model (8), suggesting that PGD 2 signaling through the DP receptor plays a pro-inflammatory role in settings of allergic inflammation. On the other hand, PGD 2 has been hypothesized to exert anti-inflammatory effects by inhibiting dendritic cell migration and T cell activation (9).The role of PGD 2 signaling through the CRTH2 receptor in allergic disease is less well established. In ...

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“…To evaluate the structural features that confer CRTH2 binding selectivity, structure-activity relationship analysis of arylacetic acid class NSAIDs as CRTH2 receptor ligands was performed. Indomethacin, sulindac sulfide, and zomepirac displaced Prostaglandin D 2 (PGD 2 ), the predominant prostanoid produced by activated mast cells, is associated with allergic diseases such as allergic asthma and atopic dermatitis (Lewis et al, 1982;Murray et al, 1986;Barr et al, 1988). The biological effects of PGD 2 are mediated by two distinct G protein-coupled receptors: the D prostanoid receptor (DP) and the recently discovered chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2).…”

Section: Introductionmentioning

confidence: 99%

Structural Determinants of Arylacetic Acid Nonsteroidal Anti-Inflammatory Drugs Necessary for Binding and Activation of the Prostaglandin D₂Receptor CRTH2

Hata¹,

Lybrand²,

Marnett³

et al. 2004

Mol Pharmacol

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The chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptor, a G protein-coupled receptor that mediates chemotaxis of inflammatory cells in response to prostaglandin D 2 (PGD 2 ), is hypothesized to play a role in Th2-mediated allergic disease. In addition to PGD 2 , CRTH2 can be activated by indomethacin, a nonselective cyclooxygenase inhibitor and widely used nonsteroidal antiinflammatory drug (NSAID). To evaluate the structural features that confer CRTH2 binding selectivity, structure-activity relationship analysis of arylacetic acid class NSAIDs as CRTH2 receptor ligands was performed. Indomethacin, sulindac sulfide, and zomepirac displaced Prostaglandin D 2 (PGD 2 ), the predominant prostanoid produced by activated mast cells, is associated with allergic diseases such as allergic asthma and atopic dermatitis (Lewis et al., 1982;Murray et al., 1986;Barr et al., 1988). The biological effects of PGD 2 are mediated by two distinct G protein-coupled receptors: the D prostanoid receptor (DP) and the recently discovered chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Despite binding PGD 2 with high affinity, the CRTH2 receptor does not share significant sequence homology with the DP or other prostanoid receptors; instead, it exhibits greatest sequence similarity to chemoattractant receptors such as the formyl peptide receptor (Hirai et al., 2001). In humans, the CRTH2 receptor is expressed on Th2 cells and eosinophils (Nagata et al., 1999a,b) which are well known to play a role in the pathogenesis of allergic diseases such as allergic asthma (Hamid et al., 2003). In vitro activation of CRTH2 stimulates chemotaxis of human Th2 cells, eosinophils and basophils and in vivo activation leads to leukocyte mobilization in rats (Hirai et al., 2001;Shichijo et al., 2003), suggesting that CRTH2 may mediate recruitment of inflammatory cells in

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The release of prostaglandin D₂ from human skin in vivo and in vitro during immediate allergic reactions

Cited by 39 publications

References 24 publications

Positioning prostanoids of the D and J series in the immunopathogenic scheme

Positioning prostanoids of the D and J series in the immunopathogenic scheme

Identification of Determinants of Ligand Binding Affinity and Selectivity in the Prostaglandin D2 Receptor CRTH2

Structural Determinants of Arylacetic Acid Nonsteroidal Anti-Inflammatory Drugs Necessary for Binding and Activation of the Prostaglandin D₂Receptor CRTH2

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The release of prostaglandin D2 from human skin in vivo and in vitro during immediate allergic reactions

Cited by 39 publications

References 24 publications

Positioning prostanoids of the D and J series in the immunopathogenic scheme

Positioning prostanoids of the D and J series in the immunopathogenic scheme

Identification of Determinants of Ligand Binding Affinity and Selectivity in the Prostaglandin D2 Receptor CRTH2

Structural Determinants of Arylacetic Acid Nonsteroidal Anti-Inflammatory Drugs Necessary for Binding and Activation of the Prostaglandin D2Receptor CRTH2

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The release of prostaglandin D₂ from human skin in vivo and in vitro during immediate allergic reactions

Structural Determinants of Arylacetic Acid Nonsteroidal Anti-Inflammatory Drugs Necessary for Binding and Activation of the Prostaglandin D₂Receptor CRTH2