8‐ iso ‐prostaglandin E ₂ induces nasal obstruction via thromboxane receptor in murine model of allergic rhinitis

Abstract

Thromboxane receptor (TP) mediates nasal obstruction, a typical symptom of allergic rhinitis. Since it has been reported that several types of eicosanoids, such as non-enzymatic oxidation product of arachidonic acid isoprostane, act as a TP ligand, there is a possibility that some other eicosanoids contribute to the TPmediated nasal obstruction. The aim of this study is to investigate the mechanisms of TP-mediated nasal obstruction. Intranasal challenges of ovalbumin (OVA) induced nasal obstruction in mice. Pharmacological blockade of TP receptor but not thromboxane A 2 synthase inhibited OVA-induced nasal obstruction. Simultaneous analysis of eicosanoids in nasal lavage fluid and the responses in trans-endothelial resistance suggested that 8-iso-prostaglandin E 2 (PGE 2 ) can be a candidate for TP ligand. Intranasal challenge of 8-iso-PGE 2 induced vascular hyperpermeability and nasal obstruction in TP receptor-dependent manner.Wholemount immunostaining of nasal septum mucosa revealed that 8-iso-PGE 2 increased plasma leakage accompanied by distention of venous sinusoids. This study shows that 8-iso-PGE 2 is a contributor in TP-mediated nasal obstruction in mice.

15‐hydroxy eicosadienoic acid is an exacerbating factor for nasal congestion in mice

“…We previously revealed that 10-time OVA stimulation induced eosinophil infiltration in nasal mucosa of BALB/c mice (Vehicle: 0.03 ± 0.01 × 10 3 cells/mm 2 , OVA: 4.15 ± 1.16 × 10 3 cells/mm 2 ). 21 We also found that the 10-time OVA stimulation induced neutrophil infiltration in nasal mucosa (Vehicle: 25.98 ± 9.75 × 10 3 cells/ mm 2 , OVA: 43.70 ± 11.31 × 10 3 cells/mm 2 , Figure 1F). We collected NALF 30 min after stimulation with OVA 10 times and measured the amount of lipid metabolites using LC-MS/MS.…”

“…Figure 1E shows the representative image of nasal mucosa. We previously revealed that 10‐time OVA stimulation induced eosinophil infiltration in nasal mucosa of BALB/c mice (Vehicle: 0.03 ± 0.01 × 10 3 cells/mm 2 , OVA: 4.15 ± 1.16 × 10 3 cells/mm 2 ) 21 . We also found that the 10‐time OVA stimulation induced neutrophil infiltration in nasal mucosa (Vehicle: 25.98 ± 9.75 × 10 3 cells/mm 2 , OVA: 43.70 ± 11.31 × 10 3 cells/mm 2 , Figure 1F).…”