Inhibition of hematopoietic prostaglandin D synthase improves allergic nasal blockage in guinea pigs.

Abstract

Although it has been suggested that prostaglandin (PG) D(2) is involved in the pathogenesis of allergic rhinitis, whether the inhibition of hematopoietic PGD(2) synthase (H-PGDS) shows beneficial effects on allergic rhinitis has been unclear. We evaluated the effects of a selective H-PGDS inhibitor, TFC-007, on nasal symptoms on Japanese cedar pollen-induced allergic rhinitis of guinea pigs. Sensitized animals were challenged with the pollen once a week. TFC-007 (30mg/kg, p.o.) given once before a challenge almost completely suppressed PGD(2) production in the nasal tissue early and late after the challenge. Although pre-treatment did not affect the incidences of sneezing and early phase nasal blockage, late phase nasal blockage was partially but significantly attenuated; however, nasal eosinophilia was not suppressed. In contrast, when TFC-007 was given once 1.5h after the challenge, the late phase response was not affected. Collectively, PGD(2) produced by H-PGDS early after an antigen challenge can participate in the induction of late phase nasal blockage, although the mechanism may be independent of eosinophil infilatration. The strategy for H-PGDS inhibition may be beneficial for allergic rhinitis therapy.

• Authors: Takeshi Nabe, Yusuke Kuriyama, Nobuaki Mizutani, Saki Shibayama, Asami Hiromoto, Masanori Fujii, Katsunao Tanaka, Shigekatsu Kohno
• Journal: Prostaglandins & other lipid mediators (Prostaglandins Other Lipid Mediat) Vol. 95 Issue 1-4 Pg. 27-34 (Aug 2011) ISSN: 1098-8823 [Print] United States
• PMID: 21601002 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Allergens
• Lipocalins
• Morpholines
• N-(4-(4-(morpholine-4-carbonyl)piperidine-1-yl)phenyl)-2-phenoxypyrimidine-5-carboxamide
• Pyrimidines
• Intramolecular Oxidoreductases
• prostaglandin R2 D-isomerase
• Prostaglandin D2

Topics

• Allergens (adverse effects)
• Animals
• Cryptomeria
• Enzyme Assays
• Eosinophilia (etiology, prevention & control)
• Eosinophils (pathology)
• Guinea Pigs
• Humans
• Intramolecular Oxidoreductases (antagonists & inhibitors, metabolism)
• Lipocalins (antagonists & inhibitors, metabolism)
• Morpholines (pharmacology, therapeutic use)
• Nasal Lavage Fluid (cytology)
• Nasal Obstruction (etiology, prevention & control)
• Pollen (adverse effects)
• Prostaglandin D2 (metabolism)
• Pyrimidines (pharmacology, therapeutic use)
• Rhinitis, Allergic, Seasonal (etiology, prevention & control)
• Sneezing (drug effects)