Pharmacology of AM211, a Potent and Selective Prostaglandin D2 Receptor Type 2 Antagonist That Is Active in Animal Models of Allergic Inflammation

2011 ◽  
Vol 338 (1) ◽  
pp. 290-301 ◽  
Author(s):  
Gretchen Bain ◽  
Daniel S. Lorrain ◽  
Karin J. Stebbins ◽  
Alex R. Broadhead ◽  
Angelina M. Santini ◽  
...  
Keyword(s):  
Animal Models ◽  
D2 Receptor ◽  
Allergic Inflammation ◽  
Receptor Type ◽  
Prostaglandin D2

scholarly journals Prostaglandin D2 Selectively Induces Chemotaxis in T Helper Type 2 Cells, Eosinophils, and Basophils via Seven-Transmembrane Receptor Crth2

2001 ◽  
Vol 193 (2) ◽  
pp. 255-262 ◽  
Author(s):  
Hiroyuki Hirai ◽  
Kazuya Tanaka ◽  
Osamu Yoshie ◽  
Kazuyuki Ogawa ◽  
Kazumi Kenmotsu ◽  
...  
Keyword(s):  
Allergic Inflammation ◽  
Allergic Diseases ◽  
Th2 Cells ◽  
Prostaglandin D2 ◽  
Dependent Manner ◽  
T Helper ◽  
Dependent Cell ◽  
Blood Eosinophils ◽  
Helper Type

Prostaglandin (PG)D2, which has long been implicated in allergic diseases, is currently considered to elicit its biological actions through the DP receptor (DP). Involvement of DP in the formation of allergic asthma was recently demonstrated with DP-deficient mice. However, proinflammatory functions of PGD2 cannot be explained by DP alone. We show here that a seven-transmembrane receptor, CRTH2, which is preferentially expressed in T helper type 2 (Th2) cells, eosinophils, and basophils in humans, serves as the novel receptor for PGD2. In response to PGD2, CRTH2 induces intracellular Ca2+ mobilization and chemotaxis in Th2 cells in a Gαi-dependent manner. In addition, CRTH2, but not DP, mediates PGD2-dependent cell migration of blood eosinophils and basophils. Thus, PGD2 is likely involved in multiple aspects of allergic inflammation through its dual receptor systems, DP and CRTH2.

scholarly journals Activation of the Prostaglandin D2 Receptor DP2/CRTH2 Increases Allergic Inflammation in Mouse

2005 ◽  
Vol 174 (6) ◽  
pp. 3703-3708 ◽  
Author(s):  
Isabelle Spik ◽  
Céline Brénuchon ◽  
Véronique Angéli ◽  
Delphine Staumont ◽  
Sébastien Fleury ◽  
...  
Keyword(s):  
D2 Receptor ◽  
Allergic Inflammation ◽  
Prostaglandin D2

scholarly journals Bradykinin B2 receptor and dopamine D2 receptor cooperatively contribute to the regulation of neutrophil adhesion to endothelial cells*

2018 ◽  
Vol 65 (3) ◽  
pp. 367-375 ◽  
Author(s):  
Anna Niewiarowska-Sendo ◽  
Anna Łabędź-Masłowska ◽  
Andrzej Kozik ◽  
Ibeth Guevara-Lora
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Dopamine D2 Receptor ◽  
Leukocyte Adhesion ◽  
D2 Receptor ◽  
Protective Role ◽  
Receptor Type ◽  
Cellular Functions ◽  
Stat3 Phosphorylation

Leukocyte adhesion to the vascular endothelium contributes to many immunological and inflammatory disorders. These processes have been shown to be mediated by bradykinin receptor type 2 (B2R) and dopamine receptor type 2 (D2R). In a previous study, we reported the formation of a B2R-D2R heterodimer, possibly altering cellular functions. Hence, in the present study, we examined the effect of co-activation of endothelial cells with B2R and D2R agonists on the interaction of these cells with neutrophils. Bradykinin, the main B2R agonist, significantly increased cell adhesion, and this effect was reversed when the endothelial cells were additionally co-treated with a selective D2R agonist, sumanirole. These results were dependent on the incubation time, showing an opposite tendency after prolonged stimulation. Significant changes in the expression of adhesion proteins, such as E-selectin and intracellular adhesion molecule 1 in endothelial cells were observed. Additionally, the cells preincubated with tumor necrosis factor-a showed decreased cell adhesion and IL-8 release after long incubation with both agonists. The modulation of cell adhesion by D2R and B2R seem to be mediated via STAT3 phosphorylation. In summary, this study demonstrated a protective role of D2R in neutrophil-endothelial cell adhesion induced by bradykinin, especially in cytokine-stimulated endothelial cells.

Single-cell analysis pinpoints distinct populations of cytotoxic CD4+ T cells and an IL-10+CD109+ TH2 cell population in nasal polyps

2021 ◽  
Vol 6 (62) ◽  
pp. eabg6356
Author(s):  
Junjie Ma ◽  
Christopher A. Tibbitt ◽  
Susanna Kumlien Georén ◽  
Murray Christian ◽  
Ben Murrell ◽  
...  
Keyword(s):  
T Cells ◽  
Nasal Polyps ◽  
Single Cell Analysis ◽  
D2 Receptor ◽  
Lymphoid Cells ◽  
Multiparameter Flow Cytometry ◽  
Prostaglandin D2 ◽  
Th2 Cell ◽  
Gata3 Expression

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a chronic inflammatory process often associated with comorbid asthma. In this study, we analyzed the transcriptomes of single T helper (TH) cells from nasal polyps of patients with CRSwNP and validated these findings using multiparameter flow cytometry. Polyp tissue contained suppressive T regulatory (Treg) cells, TH2 cells, type 2 innate lymphoid cells, and three transcriptionally distinct subsets of cytotoxic CD4+ T cells (CD4+ CTL). GATA3 expression was a feature of polyp Treg cells, whereas TH2 cells highly expressed TCN1, CD200R, and HPGDS and were enriched for genes involved in lipid metabolism. Only a portion of polyp TH2 cells expressed the prostaglandin D2 receptor CRTH2, whereas a subpopulation of CD109+CRTH2− TH2 cells expressed mRNA for common inhibitor receptors including LAG3 and TIM3 and produced IL-10. Together, we resolved the complexity of TH cells in patients with CRSwNP, identifying several distinct clusters of CD4+ CTL and a population of CD109+CRTH2− TH2 cells with putative regulatory potential.

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