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. 2023 Jan;11(1):e709.
doi: 10.1002/iid3.709.

Effect of MP-AzeFlu compared to monotherapy on COX-2, PGE2 , and EP2 gene expression in upper airway mucosa

Sonia Vicens-Artes  1 , Jordi Roca-Ferrer  1   2 , Valeria Tubita  1   3 , Mireya Fuentes  1   2 , Isam Alobid  1   2   3   4 , Antonio Valero  1   2   5 , Ferdinand Kopietz  6 , DucTung Nguyen  6 , Joaquim Mullol  1   2   3   4
Affiliations

Effect of MP-AzeFlu compared to monotherapy on COX-2, PGE2 , and EP2 gene expression in upper airway mucosa

Sonia Vicens-Artes et al. Immun Inflamm Dis. 2023 Jan.

Abstract

MP-AzeFlu (intranasal fluticasone and azelastine) has been widely studied and has demonstrated efficacy in Allergic rhinitis with a superior effect compared to these drugs administered individually; however, the mechanism by which MP-AzeFlu produces this improved clinical effect has not yet been fully explained. In this study, we investigated the effect of MP-AzeFlu and fluticasone propionate (FP) on arachidonic acid metabolism as measured by changes in regulation of cyclooxygenase (COX) isoforms, prostaglandin (PG) D2 , PGE2 , PGE2 receptor (EP) 2, and EP3. Expression of these key inflammation markers was assessed through an in vitro model of upper airway inflammation using fibroblasts derived from both healthy and inflamed upper airway mucosa. Both MP-AzeFlu and FP inhibited interleukin-1β-induced COX-2 messenger RNA (mRNA) and protein expression and PGE2 secretion in vitro. MP-AzeFlu and FP both upregulated EP2 mRNA expression, though neither upregulated EP2 protein expression. This downregulation of COX-2 and PGE2 coupled with upregulation of EP2 receptor expression reinforces the anti-inflammatory effect of MP-AzeFlu in upper airway inflammation.

Keywords: COX-2; EP2; MP-AzeFlu; PGE2; fluticasone.

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Conflict of interest statement

Joaquim Mullol is or has been a member of national and international scientific advisory boards (consulting), received fees for lectures, and grants for research projects from Allakos, AstraZeneca, Genentech‐Roche, Glenmark, GSK, Menarini, MSD, Mitsubishi‐Tanabe, MYLAN‐MEDA Pharma (Viatris), Novartis, Procter and Gamble, Sanofi‐Genzyme and Regeneron, UCB, and Uriach Group. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
MP‐AzeFlu and fluticasone effects on COX‐2 and EP2 mRNA expression at 24 h. (Panel A) MP‐AzeFlu and FP effect on COX‐2 mRNA expression. (Panel B) MP‐AzeFlu and FP effect on EP2 mRNA expression. *p < .05 compared with culture media alone; † p < .01 compared with culture media alone; ‡ p < .05 compared with IL‐1β. FC, fold change; FP, fluticasone; IL, interleukin; MP‐AzeFlu, intranasal fluticasone and azelastine; mRNA, messenger RNA.
Figure 2
Figure 2
MP‐AzeFlu and fluticasone effects on COX‐2 and EP2 protein expression and PGE2 secretion. (Panel A) Effect of MP‐AzeFlu and FP on COX‐2 protein expression. (Panel B) Effect of MP‐AzeFlu and FP on EP2 protein expression. (Panel C) Effect of MP‐AzeFlu and FP on PGE2 secretion. *p = .06 compared with culture media alone. *p < .001 compared with culture media alone; † p < .01 compared with culture media alone; ‡ p < .05 compared with IL‐1β; (§) p < .06 compared with IL‐1β. Act, β‐actin; FP, fluticasone; IL, interleukin; MP‐AzeFlu, intranasal fluticasone and azelastine.
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